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Rima Fathi Kaddurah-Daouk

Professor in Psychiatry and Behavioral Sciences
Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences
Box 102506, Durham, NC 27710
2400 Pratt St, 7th Floor Room 7018, Durham, NC 27710

Selected Publications


Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Journal Article Alzheimers Dement · April 27, 2024 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigat ... Full text Link to item Cite

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Sci Rep · March 13, 2024 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner.

Journal Article Adv Sci (Weinh) · March 2024 Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs an ... Full text Link to item Cite

Early treatment response as predictor of long-term outcome in a clinical cohort of children with ADHD.

Journal Article Eur Child Adolesc Psychiatry · February 2024 This study investigates early onset of treatment response as predictor of symptomatic and functional outcome 3 years after initiation of methylphenidate (MPH) administration in a naturalistic, clinical cohort of children and adolescents with ADHD. Children ... Full text Link to item Cite

Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders.

Journal Article Prog Lipid Res · January 2024 Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Desp ... Full text Link to item Cite

Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics.

Journal Article Nat Commun · December 20, 2023 Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated s ... Full text Link to item Cite

Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.

Journal Article Alzheimers Dement · November 2023 INTRODUCTION: The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizur ... Full text Link to item Cite

Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data.

Journal Article EBioMedicine · November 2023 BACKGROUND: Deep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. T ... Full text Link to item Cite

Circulating metabolites modulated by diet are associated with depression.

Journal Article Mol Psychiatry · September 2023 Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wi ... Full text Link to item Cite

Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.

Journal Article Sci Rep · August 23, 2023 Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer's disease. Using metabolomics, we have previously profiled oxylipins, endocan ... Full text Link to item Cite

Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

Journal Article JAMA Psychiatry · June 1, 2023 IMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. OBJECTIVE: To identify the metabolic signatures of maj ... Full text Link to item Cite

Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.

Journal Article Alzheimers Dement · February 2023 INTRODUCTION: Late-onset Alzheimer's disease (LOAD) is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, Alzheimer's disease (AD) pathology, and inexorable cognitive decline. Discovery of met ... Full text Link to item Cite

MiMeDB: the Human Microbial Metabolome Database.

Journal Article Nucleic Acids Res · January 6, 2023 The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the ... Full text Link to item Cite

Comparative Metabolomics and Microbiome Analysis of Ethanol versus OMNImet/gene•GUT Fecal Stabilization

Journal Article Analytical Chemistry · January 1, 2023 Metabolites from feces provide important insights into the functionality of the gut microbiome. As immediate freezing is not always feasible in gut microbiome studies, there is a need for sampling protocols that provide the stability of the fecal metabolom ... Full text Cite

ApoJ/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer's disease.

Journal Article Alzheimers Res Ther · December 26, 2022 BACKGROUND: Alzheimer's disease (AD) shares risk factors with cardiovascular disease (CVD) and dysregulated cholesterol metabolism is a mechanism common to both diseases. Cholesterol efflux capacity (CEC) is an ex vivo metric of plasma high-density lipopro ... Full text Link to item Cite

Interplay of the human exposome, metabolome and gut microbiome in dementia and major depression

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: The pathogenesis of dementia and depression is complex involving the interplay of genetic and environmental risk factors including diet, life-style and the gut microbiome. Dementia and depression co-occur and metabolomics studies may shed light ... Full text Cite

Interactions between brain and bile acid ratio profiles predict baseline cognitive status

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: Alterations in the brain-gut microbiome system are thought to play an important role in the development of neurodegenerative diseases. While the great majority of secreted primary bile acids (BAs) are reabsorbed in the ileum, about 5% are metab ... Full text Cite

APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.

Journal Article Alzheimers Dement · November 2022 INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We perfo ... Full text Link to item Cite

Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease.

Journal Article Commun Biol · October 8, 2022 Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzhe ... Full text Link to item Cite

Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Journal Article Alzheimers Dement · April 27, 2024 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigat ... Full text Link to item Cite

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Sci Rep · March 13, 2024 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner.

Journal Article Adv Sci (Weinh) · March 2024 Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs an ... Full text Link to item Cite

Early treatment response as predictor of long-term outcome in a clinical cohort of children with ADHD.

Journal Article Eur Child Adolesc Psychiatry · February 2024 This study investigates early onset of treatment response as predictor of symptomatic and functional outcome 3 years after initiation of methylphenidate (MPH) administration in a naturalistic, clinical cohort of children and adolescents with ADHD. Children ... Full text Link to item Cite

Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders.

Journal Article Prog Lipid Res · January 2024 Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Desp ... Full text Link to item Cite

Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics.

Journal Article Nat Commun · December 20, 2023 Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated s ... Full text Link to item Cite

Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.

Journal Article Alzheimers Dement · November 2023 INTRODUCTION: The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizur ... Full text Link to item Cite

Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data.

Journal Article EBioMedicine · November 2023 BACKGROUND: Deep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. T ... Full text Link to item Cite

Circulating metabolites modulated by diet are associated with depression.

Journal Article Mol Psychiatry · September 2023 Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wi ... Full text Link to item Cite

Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.

Journal Article Sci Rep · August 23, 2023 Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer's disease. Using metabolomics, we have previously profiled oxylipins, endocan ... Full text Link to item Cite

Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

Journal Article JAMA Psychiatry · June 1, 2023 IMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. OBJECTIVE: To identify the metabolic signatures of maj ... Full text Link to item Cite

Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.

Journal Article Alzheimers Dement · February 2023 INTRODUCTION: Late-onset Alzheimer's disease (LOAD) is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, Alzheimer's disease (AD) pathology, and inexorable cognitive decline. Discovery of met ... Full text Link to item Cite

MiMeDB: the Human Microbial Metabolome Database.

Journal Article Nucleic Acids Res · January 6, 2023 The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the ... Full text Link to item Cite

Comparative Metabolomics and Microbiome Analysis of Ethanol versus OMNImet/gene•GUT Fecal Stabilization

Journal Article Analytical Chemistry · January 1, 2023 Metabolites from feces provide important insights into the functionality of the gut microbiome. As immediate freezing is not always feasible in gut microbiome studies, there is a need for sampling protocols that provide the stability of the fecal metabolom ... Full text Cite

ApoJ/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer's disease.

Journal Article Alzheimers Res Ther · December 26, 2022 BACKGROUND: Alzheimer's disease (AD) shares risk factors with cardiovascular disease (CVD) and dysregulated cholesterol metabolism is a mechanism common to both diseases. Cholesterol efflux capacity (CEC) is an ex vivo metric of plasma high-density lipopro ... Full text Link to item Cite

Interplay of the human exposome, metabolome and gut microbiome in dementia and major depression

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: The pathogenesis of dementia and depression is complex involving the interplay of genetic and environmental risk factors including diet, life-style and the gut microbiome. Dementia and depression co-occur and metabolomics studies may shed light ... Full text Cite

Interactions between brain and bile acid ratio profiles predict baseline cognitive status

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: Alterations in the brain-gut microbiome system are thought to play an important role in the development of neurodegenerative diseases. While the great majority of secreted primary bile acids (BAs) are reabsorbed in the ileum, about 5% are metab ... Full text Cite

APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.

Journal Article Alzheimers Dement · November 2022 INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We perfo ... Full text Link to item Cite

Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease.

Journal Article Commun Biol · October 8, 2022 Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzhe ... Full text Link to item Cite

Metabolomic signatures of intravenous racemic ketamine associated remission in treatment-resistant depression: A pilot hypothesis generating study.

Journal Article Psychiatry Res · August 2022 In this pilot study (N = 9), we highlight new insights gained on ketamine's mechanism of action where we have mapped biochemical processes that are affected within 40 min of intravenous ketamine exposure. Targeting acylcarnitines, we demonstrated rapid uti ... Full text Link to item Cite

The landscape of metabolic brain alterations in Alzheimer's disease.

Journal Article Alzheimers Dement · July 13, 2022 INTRODUCTION: Alzheimer's disease (AD) is accompanied by metabolic alterations both in the periphery and the central nervous system. However, so far, a global view of AD-associated metabolic changes in the brain has been missing. METHODS: We metabolically ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

Genomics-based identification of a potential causal role for acylcarnitine metabolism in depression.

Journal Article J Affect Disord · June 15, 2022 BACKGROUND: Altered metabolism of acylcarnitines - transporting fatty acids to mitochondria - may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Men ... Full text Link to item Cite

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.

Journal Article Nat Commun · June 6, 2022 We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid speci ... Full text Link to item Cite

Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.

Journal Article Alzheimers Dement · June 2022 Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and t ... Full text Link to item Cite

Metabolomic and inflammatory signatures of symptom dimensions in major depression.

Journal Article Brain Behav Immun · May 2022 BACKGROUND: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms bu ... Full text Link to item Cite

Multi-Omics Characterization of Early- and Adult-Onset Major Depressive Disorder.

Journal Article J Pers Med · March 6, 2022 Age at depressive onset (AAO) corresponds to unique symptomatology and clinical outcomes. Integration of genome-wide association study (GWAS) results with additional “omic” measures to evaluate AAO has not been reported and may reveal novel markers of susc ... Full text Link to item Cite

Gut Microbiome-Linked Metabolites in the Pathobiology of Major Depression With or Without Anxiety-A Role for Bile Acids.

Journal Article Front Neurosci · 2022 BACKGROUND: The gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid acids that are synthesized in the liver from cholesterol and further processed by gut-ba ... Full text Link to item Cite

Network science approach elucidates integrative genomic-metabolomic signature of antidepressant response and lifetime history of attempted suicide in adults with major depressive disorder.

Journal Article Front Pharmacol · 2022 Background: Individuals with major depressive disorder (MDD) and a lifetime history of attempted suicide demonstrate lower antidepressant response rates than those without a prior suicide attempt. Identifying biomarkers of antidepressant response and lifet ... Full text Link to item Cite

The metabolic landscape of brain alterations in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: Impairment of brain glucose metabolism has been frequently described in Alzheimer's disease (AD). Moreover, the strongest predictor of the lifetime incidence of AD is the ε4 allele of APOE, a protein involved in lipid metabolism. These connecti ... Full text Cite

Investigating the importance of acylcarnitines in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: L-carnitine is present in the mammalian cells as free carnitine (FC) and acylcarnitine and the adult human brain contains almost 10% of long chain acylcarnitine. Acylcarnitines are functionally involved in β-oxidation of fatty acids and are als ... Full text Cite

A proof of concept study towards multi-omics-based computational drug repositioning in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegenerative disorder for which there currently are no disease-modifying treatments available. To accelerate the path to effective intervention strategies, drug repositioning - the application of a ... Full text Cite

Multi-omics driven predictions of response to acute phase combination antidepressant therapy: a machine learning approach with cross-trial replication.

Journal Article Transl Psychiatry · October 7, 2021 Combination antidepressant pharmacotherapies are frequently used to treat major depressive disorder (MDD). However, there is no evidence that machine learning approaches combining multi-omics measures (e.g., genomics and plasma metabolomics) can achieve cl ... Full text Link to item Cite

Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.

Journal Article Scientific reports · October 2021 It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) rando ... Full text Cite

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification.

Journal Article Sci Rep · September 23, 2021 Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, inc ... Full text Link to item Cite

Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer's disease.

Journal Article Alzheimers Res Ther · September 6, 2021 BACKGROUND: Alzheimer's disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cel ... Full text Link to item Cite

ERICH3: vesicular association and antidepressant treatment response.

Journal Article Mol Psychiatry · June 2021 Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nu ... Full text Link to item Cite

Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and pharmacoepidemiologic study.

Journal Article PLoS Med · May 2021 BACKGROUND: While Alzheimer disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association are unclear. We tested whether dysregulation of cholesterol catabolism, through its conversion to pr ... Full text Link to item Cite

Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.

Journal Article Transl Psychiatry · March 2, 2021 Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomic ... Full text Open Access Link to item Cite

Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

Journal Article Metabolomics · January 18, 2021 INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race dif ... Full text Link to item Cite

Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression.

Journal Article Brain Commun · 2021 Metabolomics in the Alzheimer's Disease Neuroimaging Initiative cohort provides a powerful tool for mapping biochemical changes in Alzheimer's disease, and a unique opportunity to learn about the association between circulating blood metabolites and brain ... Full text Link to item Cite

Microbiome for Mars: surveying microbiome connections to healthcare with implications for long-duration human spaceflight, virtual workshop, July 13, 2020.

Journal Article Microbiome · January 2021 The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on ... Full text Cite

Gut microbial molecules in behavioural and neurodegenerative conditions.

Journal Article Nat Rev Neurosci · December 2020 Mounting evidence suggests that the gut microbiome impacts brain development and function. Gut-brain connections may be mediated by an assortment of microbial molecules that are produced in the gastrointestinal tract, which can subsequently permeate many o ... Full text Link to item Cite

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.

Journal Article Cell Rep Med · November 17, 2020 Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile ... Full text Link to item Cite

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease.

Journal Article Nat Commun · November 10, 2020 Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological ... Full text Link to item Cite

Circulating ethanolamine plasmalogen indices in Alzheimer's disease: Relation to diagnosis, cognition, and CSF tau.

Journal Article Alzheimers Dement · September 2020 INTRODUCTION: Altered lipid metabolism is implicated in Alzheimer's disease (AD), but the mechanisms remain obscure. Aging-related declines in circulating plasmalogens containing omega-3 fatty acids may increase AD risk by reducing plasmalogen availability ... Full text Link to item Cite

Peripheral serum metabolomic profiles inform central cognitive impairment.

Journal Article Sci Rep · August 20, 2020 The incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profil ... Full text Link to item Cite

Influence of Sex on Platelet Reactivity in Response to Aspirin.

Journal Article J Am Heart Assoc · July 21, 2020 Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. Me ... Full text Link to item Cite

Expert insights: The potential role of the gut microbiome-bile acid-brain axis in the development and progression of Alzheimer's disease and hepatic encephalopathy.

Journal Article Med Res Rev · July 2020 Recent epidemiological and molecular studies have linked the disruption of cholesterol homeostasis to increased risk for developing Alzheimer's disease (AD). Emerging evidence also suggests that brain cholesterol accumulation contributes to the progression ... Full text Link to item Cite

Alzheimer's Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways.

Journal Article Neuron · June 3, 2020 Evidence suggests interplay among the three major risk factors for Alzheimer's disease (AD): age, APOE genotype, and sex. Here, we present comprehensive datasets and analyses of brain transcriptomes and blood metabolomes from human apoE2-, apoE3-, and apoE ... Full text Link to item Cite

Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers.

Journal Article Neurology · May 19, 2020 OBJECTIVE: To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and the amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers for AD. METHODS: Serum levels of 84 TG species w ... Full text Link to item Cite

Current concepts in pharmacometabolomics, biomarker discovery, and precision medicine

Journal Article Metabolites · April 1, 2020 Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impac ... Full text Cite

Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome.

Journal Article Nat Commun · March 2, 2020 Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group- ... Full text Link to item Cite

Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders.

Journal Article Psychol Med · March 2020 BACKGROUND: We aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls. METHODS: Patients with schizophrenia and bipolar disorders ... Full text Link to item Cite

Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma.

Journal Article J Allergy Clin Immunol · March 2020 BACKGROUND: Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed. OBJECTIVE: We sought to apply untargeted metabolomic profiling to ident ... Full text Link to item Cite

Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes.

Journal Article J Affect Disord · March 1, 2020 BACKGROUND: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profile ... Full text Link to item Cite

Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.

Journal Article CPT Pharmacometrics Syst Pharmacol · January 2020 The substantial progress made in the basic sciences of the brain has yet to be adequately translated to successful clinical therapeutics to treat central nervous system (CNS) diseases. Possible explanations include the lack of quantitative and validated bi ... Full text Link to item Cite

Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease.

Journal Article J Alzheimers Dis · 2020 BACKGROUND: Basic research has implicated intracellular cholesterol in neurons, microglia, and astrocytes in the pathogenesis of Alzheimer's disease (AD), but there is presently no assay to access intracellular cholesterol in neural cells in living people ... Full text Link to item Cite

Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology.

Journal Article Alzheimers Dement (Amst) · December 2019 INTRODUCTION: Comorbidity with metabolic diseases indicates that lipid metabolism plays a role in the etiology of Alzheimer's disease (AD). Comprehensive lipidomic analysis can provide new insights into the altered lipid metabolism in AD. METHOD: In this s ... Full text Link to item Cite

Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts.

Journal Article Sci Data · October 17, 2019 Alzheimer's disease (AD) is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related ... Full text Link to item Cite

Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.

Journal Article Transl Psychiatry · July 4, 2019 Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of ac ... Full text Open Access Link to item Cite

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

Journal Article JAMA Netw Open · July 3, 2019 IMPORTANCE: Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, ... Full text Open Access Link to item Cite

Systematic Error Removal Using Random Forest for Normalizing Large-Scale Untargeted Lipidomics Data.

Journal Article Anal Chem · March 5, 2019 Large-scale untargeted lipidomics experiments involve the measurement of hundreds to thousands of samples. Such data sets are usually acquired on one instrument over days or weeks of analysis time. Such extensive data acquisition processes introduce a vari ... Full text Link to item Cite

Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.

Journal Article Alzheimers Dement · February 2019 INTRODUCTION: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammatio ... Full text Link to item Cite

Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

Journal Article Alzheimers Dement · January 2019 INTRODUCTION: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced i ... Full text Open Access Link to item Cite

Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment.

Journal Article Front Neurosci · 2019 Major depressive disorder (MDD) is a common and disabling syndrome with multiple etiologies that is defined by clinically elicited signs and symptoms. In hopes of developing a list of candidate biological measures that reflect and relate closely to the sev ... Full text Open Access Link to item Cite

Generation and quality control of lipidomics data for the alzheimer's disease neuroimaging initiative cohort.

Journal Article Sci Data · November 20, 2018 Alzheimer's disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insi ... Full text Link to item Cite

Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders.

Journal Article J Affect Disord · October 1, 2018 BACKGROUND: Substantial research progress can be achieved if available clinical datasets can be mapped to the National Institute of Mental Health Research-Domain-Criteria (RDoC) constructs. This mapping would allow investigators to both explore more narrow ... Full text Link to item Cite

Augmentation of Physician Assessments with Multi-Omics Enhances Predictability of Drug Response: A Case Study of Major Depressive Disorder.

Journal Article IEEE Comput Intell Mag · August 2018 This work proposes a "learning-augmented clinical assessment" workflow to sequentially augment physician assessments of patients' symptoms and their socio-demographic measures with heterogeneous biological measures to accurately predict treatment outcomes ... Full text Link to item Cite

Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate.

Journal Article CPT Pharmacometrics Syst Pharmacol · August 2018 Carboxylesterase 1 (CES1) metabolizes methylphenidate and other drugs. CES1 gene variation only partially explains pharmacokinetic (PK) variability. Biomarkers predicting the PKs of drugs metabolized by CES1 are needed. We identified lipids in plasma from ... Full text Link to item Cite

Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression.

Journal Article Biochem Pharmacol · June 2018 Major depressive disorder (MDD) is the most common psychiatric illness worldwide, and it displays a striking sex-dependent difference in incidence, with two thirds of MDD patients being women. Ketamine treatment can produce rapid antidepressant effects in ... Full text Link to item Cite

The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia.

Journal Article Prog Neuropsychopharmacol Biol Psychiatry · February 2, 2018 Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to inve ... Full text Link to item Cite

Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics.

Journal Article Transl Psychiatry · January 10, 2018 Major depressive disorder (MDD) is a heterogeneous disease. Efforts to identify biomarkers for sub-classifying MDD and antidepressant therapy by genome-wide association studies (GWAS) alone have generally yielded disappointing results. We applied a metabol ... Full text Link to item Cite

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

Journal Article PLoS Med · January 2018 BACKGROUND: The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity ... Full text Link to item Cite

Sphingolipid Metabolic Pathway Impacts Thiazide Diuretics Blood Pressure Response: Insights From Genomics, Metabolomics, and Lipidomics.

Journal Article J Am Heart Assoc · December 29, 2017 BACKGROUND: Although hydrochlorothiazide (HCTZ) is a well-established first-line antihypertensive in the United States, <50% of HCTZ treated patients achieve blood pressure (BP) control. Thus, identifying biomarkers that could predict the BP response to HC ... Full text Link to item Cite

Data-driven longitudinal modeling and prediction of symptom dynamics in major depressive disorder: Integrating factor graphs and learning methods

Conference 2017 IEEE Conference on Computational Intelligence in Bioinformatics and Computational Biology, CIBCB 2017 · October 4, 2017 This paper proposes a data-driven longitudinal model that brings together factor graphs and learning methods to demonstrate a significant improvement in predictability in clinical outcomes of patients with major depressive disorder treated with antidepress ... Full text Cite

Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.

Journal Article Scientific data · October 2017 Alzheimer's disease (AD) is the most common neurodegenerative disease presenting major health and economic challenges that continue to grow. Mechanisms of disease are poorly understood but significant data point to metabolic defects that might contribute t ... Full text Cite

Metabolic network failures in Alzheimer's disease: A biochemical road map.

Journal Article Alzheimers Dement · September 2017 INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the d ... Full text Link to item Cite

The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback.

Journal Article Transl Psychiatry · August 8, 2017 Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmac ... Full text Link to item Cite

Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life.

Journal Article Neuroscience · June 14, 2017 Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, ... Full text Link to item Cite

Nomenclature for alleles of the human carboxylesterase 1 gene.

Journal Article Pharmacogenet Genomics · February 2017 Full text Link to item Cite

Pharmacometabolomic signature links simvastatin therapy and insulin resistance.

Journal Article Metabolomics · January 2017 INTRODUCTION: Statins, widely prescribed drugs for treatment of cardiovascular disease, inhibit the biosynthesis of low density lipoprotein cholesterol (LDL-C). Despite providing major benefits, sub populations of patients experience adverse effects, inclu ... Full text Link to item Cite

TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.

Journal Article Mol Psychiatry · December 2016 Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with ... Full text Link to item Cite

Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.

Journal Article Transl Psychiatry · September 20, 2016 Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reupta ... Full text Link to item Cite

A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

Journal Article Hypertension · September 2016 Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patien ... Full text Link to item Cite

Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach.

Journal Article Metabolomics · August 2016 INTRODUCTION: While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic ... Full text Link to item Cite

Pharmacometabolomics informs pharmacogenomics

Journal Article Metabolomics · July 1, 2016 Introduction: The initial decades of the twenty-first century have witnessed striking technical advances that have made it possible to detect, identify and quantitatively measure large numbers of plasma or tissue metabolites. In parallel, similar advances ... Full text Cite

Pharmacometabolomic assessment of metformin in non-diabetic, African Americans

Journal Article Frontiers in Pharmacology · June 14, 2016 Millions of individuals are diagnosed with type 2 diabetes mellitus (T2D), which increases the risk for a plethora of adverse outcomes including cardiovascular events and kidney disease. Metformin is the most widely prescribed medication for the treatment ... Full text Cite

Investigating the impact of missense mutations in hCES1 by in silico structure-based approaches

Journal Article Drug Metabolism and Personalized Therapy · June 1, 2016 Genetic variations in drug-metabolizing enzymes have been reported to influence pharmacokinetics, drug dosage and other aspects that affect therapeutic outcomes. Most particularly, non-synonymous single-nucleotide polymorphisms (nsSNPs) resulting in amino ... Full text Cite

Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

Journal Article J Alzheimers Dis · 2016 Plasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer's disease (AD) and o ... Full text Link to item Cite

Metabolomics enables precision medicine: "A White Paper, Community Perspective".

Journal Article Metabolomics · 2016 INTRODUCTION BACKGROUND TO METABOLOMICS: Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a ... Full text Link to item Cite

Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

Journal Article Metabolomics · November 21, 2015 The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily ... Full text Cite

Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.

Journal Article CPT Pharmacometrics Syst Pharmacol · November 2015 Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. ... Full text Link to item Cite

Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

Journal Article J Am Heart Assoc · October 26, 2015 BACKGROUND: While aspirin is a well-established and generally effective anti-platelet agent, considerable inter-individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement ... Full text Link to item Cite

Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans.

Journal Article Alzheimers Dement · July 2015 INTRODUCTION: Genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have been crucial in advancing the understanding of Alzheimer's disease (AD) pathophysiology. Here, we provide an update on sample collection, scientific progress and op ... Full text Link to item Cite

Metabolomic Signatures for Drug Response Phenotypes: Pharmacometabolomics Enables Precision Medicine.

Journal Article Clin Pharmacol Ther · July 2015 The scaling up of data in clinical pharmacology and the merger of systems biology and pharmacology has led to the emergence of a new discipline of Quantitative and Systems Pharmacology (QSP). This new research direction might significantly advance the disc ... Full text Link to item Cite

Synthetic cannabimimetic agents metabolized by carboxylesterases.

Journal Article Drug Test Anal · July 2015 Synthetic cannabimimetic agents are a large group of diverse compounds which act as agonists at cannabinoid receptors. Since 2004, synthetic cannabinoids have been used recreationally, although several of the compounds have been shown to cause severe toxic ... Full text Link to item Cite

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

Journal Article Ann Behav Med · February 2015 BACKGROUND: Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits. PURPOSE: The purpos ... Full text Link to item Cite

Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.

Journal Article Metabolomics · 2015 The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily ... Full text Link to item Cite

Module-based association analysis for omics data with network structure.

Journal Article PLoS One · 2015 Module-based analysis (MBA) aims to evaluate the effect of a group of biological elements sharing common features, such as SNPs in the same gene or metabolites in the same pathways, and has become an attractive alternative to traditional single bio-element ... Full text Link to item Cite

Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics.

Journal Article Pharmacogenomics · 2015 CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerabl ... Full text Link to item Cite

Quality assurance of metabolomics.

Journal Article ALTEX · 2015 Metabolomics promises a holistic phenotypic characterization of biological responses to toxicants. This technology is based on advanced chemical analytical tools with reasonable throughput, including mass-spectroscopy and NMR. Quality assurance, however - ... Full text Link to item Cite

Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

Journal Article CPT Pharmacometrics Syst Pharmacol · July 16, 2014 While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways i ... Full text Link to item Cite

Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

Journal Article Circ Cardiovasc Genet · April 2014 BACKGROUND: The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide p ... Full text Link to item Cite

Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology.

Journal Article Clin Pharmacol Ther · February 2014 Metabolomics, the study of metabolism at an "omic" level, has the potential to transform our understanding of mechanisms of drug action and the molecular basis for variation in drug response. It is now possible to define metabolic signatures of drug exposu ... Full text Link to item Cite

Integration of pharmacometabolomic and pharmacogenomic approaches reveals novel insights into antiplatelet therapy.

Journal Article Clin Pharmacol Ther · November 2013 Interindividual variability in response to antiplatelet therapy results in higher platelet reactivity as well as higher rates of cardiovascular events. Despite substantial effort, the genetic and nongenetic determinants of antiplatelet variability remain p ... Full text Link to item Cite

Pharmacometabolomics of statin response.

Journal Article Clin Pharmacol Ther · November 2013 Statins reduce risk of cardiovascular disease (CVD) by decreasing plasma low-density lipoprotein (LDL) concentrations, as well as reducing inflammation and improving endothelial function. Despite their documented efficacy, there is considerable interindivi ... Full text Link to item Cite

Purine pathway implicated in mechanism of resistance to aspirin therapy: pharmacometabolomics-informed pharmacogenomics.

Journal Article Clin Pharmacol Ther · October 2013 Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involv ... Full text Link to item Cite

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

Journal Article PLoS ONE · July 24, 2013 There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progressi ... Full text Cite

Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer's disease from normal cognitive aging.

Journal Article Acta Neuropathol Commun · June 27, 2013 BACKGROUND: A critical and as-yet unmet need in Alzheimer disease (AD) research is the development of novel markers that can identify individuals at risk for cognitive decline due to AD. This would aid intervention trials designed to slow the progression o ... Full text Link to item Cite

Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis

Journal Article Frontiers in Cellular Neuroscience · May 22, 2013 Schizophrenia (SZ) is a biochemically complex disorder characterized by widespread defects in multiple metabolic pathways whose dynamic interactions, until recently, have been difficult to examine. Rather, evidence for these alterations has been collected ... Full text Cite

Alterations in metabolic pathways and networks in Alzheimer's disease.

Journal Article Transl Psychiatry · April 9, 2013 The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We u ... Full text Link to item Cite

Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

Journal Article Transl Psychiatry · January 22, 2013 In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertralin ... Full text Link to item Cite

Pharmacometabolomics reveals racial differences in response to atenolol treatment.

Journal Article PLoS One · 2013 Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are ... Full text Link to item Cite

Pharmacometabolomic signature of ataxia SCA1 mouse model and lithium effects.

Journal Article PLoS One · 2013 We have shown that lithium treatment improves motor coordination in a spinocerebellar ataxia type 1 (SCA1) disease mouse model (Sca1(154Q/+)). To learn more about disease pathogenesis and molecular contributions to the neuroprotective effects of lithium, w ... Full text Link to item Cite

Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway.

Journal Article PLoS One · 2013 Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective ... Full text Open Access Link to item Cite

Purine pathway implicated in mechanism of resistance to aspirin therapy: Pharmacometabolomics-informed pharmacogenomics

Journal Article Clinical Pharmacology and Therapeutics · 2013 Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involv ... Full text Cite

Enantioselective determination of methylphenidate and ritalinic acid in whole blood from forensic cases using automated solid-phase extraction and liquid chromatography-tandem mass spectrometry.

Journal Article J Anal Toxicol · October 2012 A chiral liquid chromatography tandem mass spectrometry (LC-MS-MS) method was developed and validated for quantifying methylphenidate and its major metabolite ritalinic acid in blood from forensic cases. Blood samples were prepared in a fully automated sys ... Full text Link to item Cite

Impaired plasmalogens in patients with schizophrenia.

Journal Article Psychiatry Res · August 15, 2012 Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmogens. An earlier study found differences in plasma phospholipids betw ... Full text Link to item Cite

Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.

Journal Article Pharmacogenet Genomics · April 2012 OBJECTIVE: We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by single-nucleotide polymorphism (SNP) imputation of metabolomic-derived pathway data on a 'scaffolding' of genome-wide associ ... Full text Link to item Cite

Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart failure and major depressive disorder.

Journal Article J Cardiovasc Transl Res · February 2012 The omega-3 fatty acid (FA) concentration is low in patients with coronary heart disease (CHD). Supplement of omega-3 FA improves cardiovascular outcomes in patients with CHD and heart failure (HF). However, plasma omega-3 FA and its role for prognosis in ... Full text Link to item Cite

Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile.

Journal Article Sci Rep · 2012 Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the d ... Full text Link to item Cite

Associations between purine metabolites and clinical symptoms in schizophrenia.

Journal Article PLoS One · 2012 BACKGROUND: The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology o ... Full text Link to item Cite

Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment.

Journal Article PLoS One · 2012 UNLABELLED: Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolom ... Full text Link to item Cite

3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia.

Journal Article Int J Neuropsychopharmacol · July 2011 One branch of the tryptophan catabolic cascade is the kynurenine pathway, which produces neurotoxic [3-hydroxykynurenine (3-OHKY), quinolinic acid] and neuroinhibitory (kynurenic acid) compounds. Kynurenic acid acts as a competitive antagonist at the glyci ... Full text Link to item Cite

Metabolomic changes in autopsy-confirmed Alzheimer's disease.

Journal Article Alzheimers Dement · May 2011 BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insight ... Full text Link to item Cite

Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.

Journal Article PLoS One · 2011 BACKGROUND: The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and ... Full text Link to item Cite

Enteric microbiome metabolites correlate with response to simvastatin treatment.

Journal Article PLoS One · 2011 Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping p ... Full text Link to item Cite

Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

Journal Article Transl Psychiatry · 2011 The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned ... Full text Link to item Cite

Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.

Journal Article Clin Pharmacol Ther · January 2011 Major depressive disorder (MDD) is a common psychiatric disease. Selective serotonin reuptake inhibitors (SSRIs) are an important class of drugs used in the treatment of MDD. However, many patients do not respond adequately to SSRI therapy. We used a pharm ... Full text Link to item Cite

Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

Journal Article Transl Psychiatry · 2011 The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned ... Full text Link to item Cite

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Journal Article Mol Psychiatry · September 2010 Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant b ... Full text Link to item Cite

Metabolomic differences in heart failure patients with and without major depression.

Journal Article J Geriatr Psychiatry Neurol · June 2010 Metabolomics is an emerging technology that allows researchers to characterize hundreds of small molecules that comprise the metabolome. We sought to determine metabolic differences in depressed and nondepressed participants. The sample consisted of a depr ... Full text Link to item Cite

Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions.

Journal Article Metabolomics · June 1, 2010 Despite the long-established therapeutic efficacy of lithium in the treatment of bipolar disorder (BPD), its molecular mechanism of action remains elusive. Newly developed stable isotope-resolved metabolomics (SIRM) is a powerful approach that can be used ... Full text Link to item Cite

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.

Journal Article Metabolomics · June 2010 Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also ... Full text Link to item Cite

Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

Journal Article PLoS One · March 3, 2010 BACKGROUND: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. METHODOLOGY/PRINCIPA ... Full text Open Access Link to item Cite

Metabolomics: A global biochemical approach to the discovery of biomarkers for psychiatric disorders

Journal Article · December 1, 2009 A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal or pathogenic processes, as well as responses to therapeutic interventions. The discovery of biomarkers for psychiatric disorders and their incorporation i ... Full text Cite

Opioid use affects antioxidant activity and purine metabolism: preliminary results.

Journal Article Hum Psychopharmacol · December 2009 OBJECTIVE: More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant ... Full text Link to item Cite

Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study.

Journal Article Psychopharmacology (Berl) · October 2009 BACKGROUND: Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. OBJECTIVE: We examined the differences in metabolites related to the tyrosine, tryptophan, purine, an ... Full text Link to item Cite

Metabolomics tools for identifying biomarkers for neuropsychiatric diseases.

Journal Article Neurobiol Dis · August 2009 The repertoire of biochemicals (or small molecules) present in cells, tissue, and body fluids is known as the metabolome. Today, clinicians utilize only a very small part of the information contained in the metabolome, as revealed by the quantification of ... Full text Link to item Cite

Metabolomics: a global biochemical approach to the study of central nervous system diseases.

Journal Article Neuropsychopharmacology · January 2009 Metabolomics, the omics science of biochemistry, is a global approach to understanding regulation of metabolic pathways and metabolic networks of a biological system. Metabolomics complements data derived from genomics, transcriptomics, and proteomics to a ... Full text Link to item Cite

Metabolomic Mapping of Atypical Effects in Schizophrenia

Conference DRUG METABOLISM REVIEWS · 2009 Cite

Metabolomics: a global biochemical approach to drug response and disease.

Journal Article Annu Rev Pharmacol Toxicol · 2008 Metabolomics is the study of metabolism at the global level. This rapidly developing new discipline has important potential implications for pharmacologic science. The concept that metabolic state is representative of the overall physiologic status of the ... Full text Link to item Cite

Metabolomics: Concepts and potential neuroscience applications

Journal Article · December 1, 2007 Metabolomics-the-omics face of biochemistry-may be considered as a global approach to capturing and understanding the metabolic network of a biological system. Metabolomics expands and complements the data obtained from the other three major-omics fields-g ... Full text Cite

Metabolomic mapping of atypical antipsychotic effects in schizophrenia.

Journal Article Mol Psychiatry · October 2007 Schizophrenia is associated with impairments in neurotransmitter systems and changes in neuronal membrane phospholipids. Several atypical antipsychotic drugs induce weight gain and hypertriglyceridemia. To date, there has not been a comprehensive evaluatio ... Full text Link to item Cite

The metabolomics standards initiative (MSI)

Journal Article Metabolomics · September 1, 2007 In 2005, the Metabolomics Standards Initiative has been formed. An outline and general introduction is provided to inform about the history, structure, working plan and intentions of this initiative. Comments on any of the suggested minimal reporting stand ... Full text Cite

The metabolomics standards initiative.

Journal Article Nat Biotechnol · August 2007 Full text Link to item Cite

A preliminary metabolomic analysis of older adults with and without depression.

Journal Article Int J Geriatr Psychiatry · May 2007 BACKGROUND: Metabolomics, the global science of biochemistry, is an emerging field that enables detection and quantification of small molecules involved in metabolic and signaling pathways. Metabolic signatures for disease and its treatment could provide v ... Full text Link to item Cite

Metabolomics in the study of aging and caloric restriction

Journal Article Methods in Molecular Biology · April 5, 2007 Metabolomics is the systematic and theoretically comprehensive study of the small molecules that comprise a biological sample, e.g., sera or plasma. Metabolomics, in conjunction with other "-omics" approaches, offers a new window onto the study of aging an ... Full text Cite

High-performance liquid chromatography separations coupled with coulometric electrode array detectors: a unique approach to metabolomics.

Journal Article Methods Mol Biol · 2007 Metabolomics is the systematic and theoretically comprehensive study of the small molecules that comprise a biological sample, e.g., sera or plasma. The primary analytical tools used in metabolomics are nuclear magnetic resonance and mass spectroscopy. We ... Full text Link to item Cite

Metabolomics in the study of aging and caloric restriction.

Journal Article Methods Mol Biol · 2007 Metabolomics is the systematic and theoretically comprehensive study of the small molecules that comprise a biological sample, e.g., sera or plasma. Metabolomics, in conjunction with other "-omics" approaches, offers a new window onto the study of aging an ... Full text Link to item Cite

ANYL 288-Metabolomics for mapping disease signatures and drug response phenotypes

Journal Article ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2007 Cite

Metabolic profiling of patients with schizophrenia.

Journal Article PLoS Med · August 2006 Kaddurah-Daouk discusses a new study that found that patients with schizophrenia have an abnormal cerebrospinal fluid composition. In half of the patients, the composition returned to normal with antipsychotic therapy. ... Full text Link to item Cite

Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results.

Journal Article Brief Bioinform · June 2006 Informatics standards and controlled vocabularies are essential for allowing information technology to help exchange, manage, interpret and compare large data collections. In a rapidly evolving field, the challenge is to work out how best to describe, but ... Full text Link to item Cite

Biomarkers for amyotrophic lateral sclerosis.

Journal Article Expert Rev Mol Diagn · May 2006 Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. ALS is a fatal neurodegenerative disease and clinical diagnosis typically takes many months to complete. Early disease diagnosis through the use of biomarkers may aid in c ... Full text Link to item Cite

Establishing reporting standards for metabolomic and metabonomic studies: a call for participation.

Journal Article OMICS · 2006 Metabolite concentrations in cellular systems are very much dependent on the physiological, environmental, and genetic status of an organism and are regarded as the ultimate result of cellular regulation, resulting in the visible phenotypes. Therefore, the ... Full text Link to item Cite

Metabolomics: A new approach towards identifying biomarkers and therapeutic targets in CNS disorders

Journal Article · December 1, 2005 Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS) are poorly understood disorders for which there are no effective therapies. Both genetic and environ ... Full text Cite

Metabolomic analysis and signatures in motor neuron disease.

Journal Article Metabolomics · 2005 Motor neuron diseases (MND) are a heterogeneous group of disorders that includes amyotrophic lateral sclerosis (ALS) and result in death of motor neurons. These diseases may produce characteristic perturbations of the metabolome, the collection of small-mo ... Full text Link to item Cite

Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation.

Journal Article J Neurochem · April 2001 Several lines of evidence implicate excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS). Transgenic mice with a superoxide dismutase mutation (G93A) have been utilized as an animal model of familial ALS (FALS). We examined the ... Full text Link to item Cite

Creatine and creatinine metabolism.

Journal Article Physiol Rev · July 2000 The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzym ... Full text Link to item Cite

Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.

Journal Article J Neurosci · June 15, 2000 Huntington's disease (HD) is a progressive neurodegenerative illness for which there is no effective therapy. We examined whether creatine, which may exert neuroprotective effects by increasing phosphocreatine levels or by stabilizing the mitochondrial per ... Full text Link to item Cite

Neuroprotective effects of creatine administration against NMDA and malonate toxicity.

Journal Article Brain Res · March 31, 2000 We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creat ... Full text Link to item Cite

Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent

Journal Article Neuroscience Research Communications · 2000 The discovery of mutations in the human SOD1 gene encoding (Cu, Zn SOD) in patients with familial amyotrophic lateral sclerosis (ALS) has made possible the development of etiological models of the disease. Expression of mutant SOD1 genes in transgenic mice ... Full text Cite

The neuroprotective properties of creatine in animal models of neurodegenerative diseases

Conference CREATINE: FROM BASIC SCIENCE TO CLINICAL APPLICATION · 2000 Cite

Creatine and cyclocreatine attenuate MPTP neurotoxicity.

Journal Article Exp Neurol · May 1999 Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+ ... Full text Link to item Cite

Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.

Journal Article Nat Med · March 1999 Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with ... Full text Link to item Cite

Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase.

Journal Article Int J Cancer · September 25, 1998 Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine), an analog of creatine and a substrate for creatine kinase (EC 2.7.3.2), inhibits the stimulated motility of tumor cells which possess creatine kinase. A2058-055 human melanoma cells, transfected with a ... Full text Link to item Cite

Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism.

Journal Article In Vivo · 1998 When rats bearing the 13,762 mammary carcinoma were treated with intravenously administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation, the tumor growth ... Link to item Cite

Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease.

Journal Article J Neurosci · January 1, 1998 The gene defect in Huntington's disease (HD) may result in an impairment of energy metabolism. Malonate and 3-nitropropionic acid (3-NP) are inhibitors of succinate dehydrogenase that produce energy depletion and lesions that closely resemble those of HD. ... Full text Link to item Cite

Synthesis and creatine kinase inhibitory activity of nonhydrolyzable analogs of phosphocreatine

Journal Article Bioorganic and Medicinal Chemistry Letters · April 22, 1997 The first hydrolytically stable phosphocreatine (CrP) analogs with a CH2-P isostere in place of the NH-P linkage have been synthesized and found to inhibit creatine kinase (CK) with potencies in the low mM range. The closest structural analog of CrP, 2, wa ... Full text Cite

Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters.

Journal Article J Mol Cell Cardiol · April 1996 To study the contribution of myocardial energy reserve to the deterioration of cardiac function during the development of heart failure, we defined energy reserve via the creatine kinase (CK) reaction and the isovolumic contractile performance in hearts of ... Full text Link to item Cite

Specific targeting of tumor cells by the creatine analog cyclocreatine

Journal Article International Journal of Oncology · January 1, 1996 Creatine kinase (CK) an enzyme involved in cellular ATP homeostasis has been implicated in tumorigenesis. Cyclocreatine (CCr) a CK substrate analog was shown to be cytotoxic to a broad spectrum of solid tumors. We have measured and compared the CK activity ... Full text Cite

The synthetic phosphagen cyclocreatine phosphate inhibits the growth of a broad spectrum of solid tumors.

Journal Article Anticancer Res · 1996 BACKGROUND: The brain isoform of creatine kinase (CKBB), an enzyme involved in energy metabolism, has been implicated in cellular transformation process. Cyclocreatine (CCr), a creatine kinase (CK) substrate analogue, was shown to inhibit the growth of a b ... Link to item Cite

Creatine and phosphocreatine analogs: anticancer activity and enzymatic analysis.

Journal Article Oncol Res · 1996 The brain isoform of creatine kinase has been implicated in cellular transformation processes. Cyclocreatine, a creatine kinase substrate analog, was previously shown to be cytotoxic to a broad spectrum of solid tumors. We have synthesized, enzymatically c ... Link to item Cite

Microtubule stabilization and potentiation of taxol activity by the creatine analog cyclocreatine.

Journal Article Anticancer Drugs · June 1995 Creatine kinase (CK), a key enzyme of cellular energetics, has been implicated in tumorigenesis. Cyclocreatine (CCr), which forms a stable phosphagen with a reduced rate of ATP regeneration through CK, inhibits the growth of many solid tumors. We report th ... Full text Link to item Cite

Enhancement of cardiac function by cyclocreatine in models of cardiopulmonary bypass.

Journal Article J Mol Cell Cardiol · April 1995 This study tests the hypothesis that the administration of cyclocreatine prior to global ischemia enhances recovery of cardiac function during reperfusion. Two models were used. First, in a Langendorff-working heart model of normothermic cardioplegic arres ... Full text Link to item Cite

Antiproliferative effects of cyclocreatine on human prostatic carcinoma cells.

Journal Article Anticancer Res · 1995 Creatine kinase (CK; EC 2.7.3.2) isoenzymes and their substrates have an important function in cellular energy generation and utilization. The brain isoform (CK-BB) has been implicated in cellular transformation processes involving the oncogenic products o ... Link to item Cite

Cyclocreatine in cancer chemotherapy.

Journal Article Cancer Chemother Pharmacol · 1995 Cyclocreatine, an analog of creatine, is an efficient substrate for creatine kinase, but its phosphorylated form is a poor phosphate donor in comparison with creatine phosphate. Cyclocreatine was not very cytotoxic upon 24 h of exposure of human SW2 small- ... Full text Link to item Cite

Cell cycle studies of cyclocreatine, a new anticancer agent.

Journal Article Cancer Res · October 1, 1994 Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK), exhibits antitumor activity in vitro and in vivo. To address its mechanism of action, we have examined its effects on tumor cell proliferation, viability, and cell cycle progression. Comple ... Link to item Cite

Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells.

Journal Article J Natl Cancer Inst · April 20, 1994 BACKGROUND: The creatine kinase (CK) isozymes and their substrates, creatine and creatine phosphate, are believed to play a pivotal role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, and brain. Th ... Full text Link to item Cite

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses.

Journal Article Antiviral Res · April 1994 The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been ... Full text Link to item Cite

Enhancement of the recovery of rat hearts after prolonged cold storage by cyclocreatine phosphate.

Journal Article Transplantation · March 27, 1994 The present study determined whether the administration of cyclocreatine phosphate (CCrP) prior to ischemia can enhance the recovery of rat hearts hypothermically preserved for a prolonged period. Rats (n = 6 per group) were injected intravenously with 1 m ... Full text Link to item Cite

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.

Journal Article Cancer Res · July 1, 1993 In an effort to investigate the role of creatine kinase and its substrates in malignancy we have tested the effect of cyclocreatine [1-carboxymethyl-2-iminoimidazolidine (CCr)] on the growth of tumor cells in vitro and in vivo. CCr is phosphorylated by cre ... Link to item Cite

Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a.

Journal Article Mol Cell Biol · April 1990 Brain creatine kinase is a major enzyme of cellular energy metabolism. It is overexpressed in a wide range of tumor cell lines and is used as a tumor marker. We reported recently that the promoter of the human gene has a strong sequence similarity to the a ... Full text Link to item Cite

Isolation of a functional human gene for brain creatine kinase.

Journal Article J Biol Chem · February 15, 1988 There is evidence that the gene for the B isozyme of creatine kinase is regulated during cell differentiation, is under hormonal control, and is activated in a small cell lung carcinoma. In order to investigate further the mechanisms of these processes, th ... Link to item Cite

Activation and repression of mammalian gene expression by the c-myc protein.

Journal Article Genes Dev · June 1987 One mechanism by which nuclear-localized oncogenes might transform cells is through an ability to regulate gene expression. We show that the c-myc protein stimulates the level of appropriately initiated expression from the human heat shock protein 70 (hsp7 ... Full text Link to item Cite

Purification of the HhaII restriction endonuclease from an overproducer Escherichia coli clone.

Journal Article J Biol Chem · December 5, 1985 An Escherichia coli K12 strain carrying the HhaII methylase and restriction genes on two separate compatible plasmids, pSK5 and pSK7, is used to overproduce the restriction endonuclease. Plasmid pSK5 expresses the methylase gene constitutively from its chl ... Link to item Cite

Catalytic properties of the HhaII restriction endonuclease.

Journal Article J Biol Chem · December 5, 1985 The catalytic properties of the HhaII restriction endonuclease were studied using plasmid pSK11 DNA containing a single 5'-G-A-N-T-C HhaII cleavage site as substrate. Reactions were followed by two methods: 1) gel electrophoretic analysis of nicked circula ... Link to item Cite