Scholars@Duke
Michael P. Vitek

Michael P. Vitek

Adjunct Associate Professor in Neurology
Neurology, Behavioral Neurology
Michael.Vitek@duke.edu
Duke Box 2900, Durham, NC 27710
201D Bryan Res Bldg, Durham, NC
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Selected Publications

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Journal Article J Alzheimers Dis · 2024 Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle ... Full text Link to item Cite

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers.

Journal Article Pharmaceutics · March 28, 2023 Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric inf ... Full text Link to item Cite

PPP2CA Is a Novel Therapeutic Target in Neuroblastoma Cells That Can Be Activated by the SET Inhibitor OP449.

Journal Article Front Oncol · 2022 Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and has a poor prognosis in high-risk cases, requiring novel therapies. Pathways that depend on phospho-signaling maintain the aggressiveness of NB. Protein phosphatase 2 (PP2A) wi ... Full text Link to item Cite

Apolipoprotein E mimetic peptide COG1410 combats pandrug-resistant Acinetobacter baumannii.

Journal Article Front Microbiol · 2022 The emergence of pandrug-resistant bacteria breaks through the last line of defense and raises fear among people of incurable infections. In the post-antibiotic era, the pharmaceutical field turns to seek non-conventional anti-infective agents. Antimicrobi ... Full text Link to item Cite

Caspase-1 and the inflammasome promote polycystic kidney disease progression.

Journal Article Front Mol Biosci · 2022 We and others have previously shown that the presence of renal innate immune cells can promote polycystic kidney disease (PKD) progression. In this study, we examined the influence of the inflammasome, a key part of the innate immune system, on PKD. The in ... Full text Open Access Link to item Cite

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.

Journal Article ASN Neuro · 2021 Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-media ... Full text Link to item Cite

Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma.

Journal Article Eur J Pharmacol · September 5, 2020 As SET protein is overexpressed and PP2A activity is reduced in oral squamous cell carcinoma (OSCC), this study aimed to assess the effects induced by OP449, a PP2A activator/SET inhibitor, on OSCC cells in vitro, and its potential either isolated or combi ... Full text Link to item Cite

Translational animal models for Alzheimer's disease: An Alzheimer's Association Business Consortium Think Tank.

Journal Article Alzheimers Dement (N Y) · 2020 Over 5 million Americans and 50 million individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated with AD currently has no cure. Although clinical trials in patients are ultimately required to find safe and effecti ... Full text Open Access Link to item Cite

Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.

Journal Article Transl Stroke Res · December 2018 Subarachnoid hemorrhage (SAH) is a neurologically destructive stroke in which early brain injury (EBI) plays a pivotal role in poor patient outcomes. Expanding upon our previous work, multiple techniques and methods were used in this preclinical study to f ... Full text Link to item Cite

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis.

Journal Article Mol Cancer Res · March 2018 Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique ... Full text Link to item Cite

Apolipoprotein E-Mimetic Peptide COG1410 Promotes Autophagy by Phosphorylating GSK-3β in Early Brain Injury Following Experimental Subarachnoid Hemorrhage.

Journal Article Front Neurosci · 2018 COG1410, a mimetic peptide derived from the apolipoprotein E (apoE) receptor binding region, exerts positive effect on neurological deficits in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). Currently the neuroprotective effect ... Full text Link to item Cite

OP449 inhibits breast cancer growth without adverse metabolic effects.

Journal Article Endocr Relat Cancer · October 2017 Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates ... Full text Link to item Cite

Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage.

Journal Article Transl Stroke Res · June 2017 Apolipoprotein E (ApoE)-mimetic peptides have been demonstrated to be beneficial in secondary brain injury following experimental subarachnoid hemorrhage (SAH). However, the molecular mechanisms underlying these benefits in SAH models have not been clearly ... Full text Link to item Cite

Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression.

Journal Article Ann Rheum Dis · March 2017 OBJECTIVES: Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two ... Full text Link to item Cite

The Role of PP2A inhibitor SET/I2PP2A in Gastric Cancer

Conference JOURNAL OF PHARMACOLOGICAL SCIENCES · March 1, 2017 Link to item Cite

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

Journal Article J Neurotrauma · February 15, 2017 Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several model ... Full text Link to item Cite

Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia.

Journal Article Oncotarget · December 20, 2016 Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated i ... Full text Link to item Cite

Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity.

Journal Article Oncotarget · August 30, 2016 Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential rol ... Full text Link to item Cite

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Journal Article J Alzheimers Dis · 2024 Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle ... Full text Link to item Cite

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers.

Journal Article Pharmaceutics · March 28, 2023 Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric inf ... Full text Link to item Cite

PPP2CA Is a Novel Therapeutic Target in Neuroblastoma Cells That Can Be Activated by the SET Inhibitor OP449.

Journal Article Front Oncol · 2022 Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and has a poor prognosis in high-risk cases, requiring novel therapies. Pathways that depend on phospho-signaling maintain the aggressiveness of NB. Protein phosphatase 2 (PP2A) wi ... Full text Link to item Cite

Apolipoprotein E mimetic peptide COG1410 combats pandrug-resistant Acinetobacter baumannii.

Journal Article Front Microbiol · 2022 The emergence of pandrug-resistant bacteria breaks through the last line of defense and raises fear among people of incurable infections. In the post-antibiotic era, the pharmaceutical field turns to seek non-conventional anti-infective agents. Antimicrobi ... Full text Link to item Cite

Caspase-1 and the inflammasome promote polycystic kidney disease progression.

Journal Article Front Mol Biosci · 2022 We and others have previously shown that the presence of renal innate immune cells can promote polycystic kidney disease (PKD) progression. In this study, we examined the influence of the inflammasome, a key part of the innate immune system, on PKD. The in ... Full text Open Access Link to item Cite

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.

Journal Article ASN Neuro · 2021 Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-media ... Full text Link to item Cite

Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma.

Journal Article Eur J Pharmacol · September 5, 2020 As SET protein is overexpressed and PP2A activity is reduced in oral squamous cell carcinoma (OSCC), this study aimed to assess the effects induced by OP449, a PP2A activator/SET inhibitor, on OSCC cells in vitro, and its potential either isolated or combi ... Full text Link to item Cite

Translational animal models for Alzheimer's disease: An Alzheimer's Association Business Consortium Think Tank.

Journal Article Alzheimers Dement (N Y) · 2020 Over 5 million Americans and 50 million individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated with AD currently has no cure. Although clinical trials in patients are ultimately required to find safe and effecti ... Full text Open Access Link to item Cite

Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.

Journal Article Transl Stroke Res · December 2018 Subarachnoid hemorrhage (SAH) is a neurologically destructive stroke in which early brain injury (EBI) plays a pivotal role in poor patient outcomes. Expanding upon our previous work, multiple techniques and methods were used in this preclinical study to f ... Full text Link to item Cite

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis.

Journal Article Mol Cancer Res · March 2018 Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique ... Full text Link to item Cite

Apolipoprotein E-Mimetic Peptide COG1410 Promotes Autophagy by Phosphorylating GSK-3β in Early Brain Injury Following Experimental Subarachnoid Hemorrhage.

Journal Article Front Neurosci · 2018 COG1410, a mimetic peptide derived from the apolipoprotein E (apoE) receptor binding region, exerts positive effect on neurological deficits in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). Currently the neuroprotective effect ... Full text Link to item Cite

OP449 inhibits breast cancer growth without adverse metabolic effects.

Journal Article Endocr Relat Cancer · October 2017 Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates ... Full text Link to item Cite

Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage.

Journal Article Transl Stroke Res · June 2017 Apolipoprotein E (ApoE)-mimetic peptides have been demonstrated to be beneficial in secondary brain injury following experimental subarachnoid hemorrhage (SAH). However, the molecular mechanisms underlying these benefits in SAH models have not been clearly ... Full text Link to item Cite

Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression.

Journal Article Ann Rheum Dis · March 2017 OBJECTIVES: Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two ... Full text Link to item Cite

The Role of PP2A inhibitor SET/I2PP2A in Gastric Cancer

Conference JOURNAL OF PHARMACOLOGICAL SCIENCES · March 1, 2017 Link to item Cite

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

Journal Article J Neurotrauma · February 15, 2017 Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several model ... Full text Link to item Cite

Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia.

Journal Article Oncotarget · December 20, 2016 Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated i ... Full text Link to item Cite

Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity.

Journal Article Oncotarget · August 30, 2016 Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential rol ... Full text Link to item Cite

An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage.

Journal Article Neurosci Lett · August 3, 2016 This study investigated the neuroprotective effects of COG1410, an apoliporotein E (apoE)-derived mimic peptide, against early brain injury (EBI) after subarachnoid hemorrhage (SAH). SAH was induced in C57BL/6J mice (n=68) by endovascular perforation. Mice ... Full text Link to item Cite

Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury.

Journal Article J Neurotrauma · January 15, 2016 The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic pe ... Full text Link to item Cite

Abstract A092: Surpassing the emerging immune-checkpoint inhibitor market

Journal Article Cancer Immunology Research · January 1, 2016 AbstractAntibodies to checkpoint inhibitors like PD-1, PD-L1 and CTLA4 activate resident Cytotoxic T-Lymphocytes to attack and kill tumor cells. The main mechanism that they employ to kill the cancer cells i ... Full text Open Access Cite

Inhibition of Pten deficient Castration Resistant Prostate Cancer by Targeting of the SET - PP2A Signaling axis.

Journal Article Sci Rep · November 13, 2015 The PP2A signaling axis regulates multiple oncogenic drivers of castration resistant prostate cancer (CRPC). We show that targeting the endogenous PP2A regulator, SET (I2PP2A), is a viable strategy to inhibit prostate cancers that are resistant to androgen ... Full text Open Access Link to item Cite

The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma.

Journal Article J Vet Med Sci · November 2015 Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which ... Full text Link to item Cite

The N-terminal Set-β Protein Isoform Induces Neuronal Death.

Journal Article J Biol Chem · May 22, 2015 Set-β protein plays different roles in neurons, but the diversity of Set-β neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-β are altered in Alzheimer disease, cleavage of Set-β leads to ... Full text Link to item Cite

Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease.

Journal Article J Neurosci · April 15, 2015 The pathogenesis of Alzheimer's disease (AD) is a critical unsolved question; and although recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction a ... Full text Link to item Cite

The impact of human and mouse differences in NOS2 gene expression on the brain's redox and immune environment.

Journal Article Mol Neurodegener · November 17, 2014 BACKGROUND: Mouse models are used in the study of human disease. Despite well-known homologies, the difference in immune response between mice and humans impacts the application of data derived from mice to human disease outcomes. Nitric oxide synthase-2 ( ... Full text Link to item Cite

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

Journal Article J Neuropathol Exp Neurol · August 2014 Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that ... Full text Link to item Cite

ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.

Journal Article J Neurosci Res · July 2014 Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivi ... Full text Open Access Link to item Cite

Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer.

Journal Article Mol Cancer Res · June 2014 UNLABELLED: Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new t ... Full text Link to item Cite

Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia.

Journal Article Clin Cancer Res · April 15, 2014 PURPOSE: The SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia. We evaluated the efficacy of SET antagonism in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cell lines, a murine leukemi ... Full text Link to item Cite

Apolipoprotein E plays a key role against cryptosporidial infection in transgenic undernourished mice.

Journal Article PLoS One · 2014 Apolipoliprotein E (apoE), a critical targeting protein in lipid homeostasis, has been found to have immunoinflammatory effects on murine models of infection and malnutrition. The effects of apoE in undernourished and Cryptosporidium parvum-infected mice h ... Full text Link to item Cite

The study of the neuroprotective activity of the apolipoprotein e peptide mimetic Cog1410 in transgenic strains of Drosophila melanogaster

Journal Article Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry · January 1, 2014 The neuroprotective activity of peptide mimetic of apolipoprotein E (apoE) Cog1410, containing the amino acid sequence of the apoE receptor-binding domain, has been investigated in transgenic Drosophila melanogaster strains expressing human APP and beta-se ... Full text Cite

[Investigation of neuroprotective activity of apolipoprotein E peptide mimetic Cog1410 in transgenic lines of Drosophila melanogaster].

Journal Article Biomed Khim · 2014 The neuroprotective activity of apolipoprotein E (apoE) peptide mimetic Cog1410, containing amino acid sequence of the receptor-binding domain apoE, has been investigated in transgenic lines of Drosophila melanogaster expressing human APP and beta-secretas ... Full text Link to item Cite

OP449, a Novel SET Antagonist, Is Cytotoxic To Leukemia Cells and Enhances Efficacy Of Tyrosine Kinase Inhibitors In Drug-Resistant Myeloid Leukemias

Conference Blood · November 15, 2013 AbstractBackgroundThe SET oncoprotein, an inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia cells, preventi ... Full text Cite

A REMYELINATING AGENT FOR TREATMENT OF MULTIPLE SCLEROSIS

Conference MULTIPLE SCLEROSIS JOURNAL · September 1, 2013 Link to item Cite

Abstract 510: Activation of PP2A by SET antagonism destabilizes c-Myc and inhibits breast cancer growth.

Conference Cancer Research · April 15, 2013 AbstractBackground: Protein phosphorylation plays an important role in regulating cellular signaling and deregulation of this process can contribute to many aberrant cellular behaviors, including those that ... Full text Cite

Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

Journal Article J Neurol Neurophysiol · April 2013 OBJECTIVE: Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimeti ... Full text Open Access Link to item Cite

ApolipoproteinE mimetic peptides improve outcome after focal ischemia.

Journal Article Exp Neurol · March 2013 Growing clinical evidence implicates isoform-specific effects of apolipoprotein E (apoE) in reducing neuroinflammation and mediating adaptive responses following ischemic and traumatic brain injury. However, the intact apoE holoprotein does not cross the b ... Full text Link to item Cite

The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features.

Journal Article Neurodegener Dis · 2013 BACKGROUND: Amyloid-β (Aβ) peptides derive from the amyloid precursor protein (APP) and play a pivotal role in Alzheimer's disease (AD) pathogenesis. Our previous work showed that the APP intracellular domain (AICD), which is produced simultaneously with A ... Full text Link to item Cite

A potential therapeutic application of SET/I2PP2A inhibitor OP449 for canine T-cell lymphoma.

Journal Article J Vet Med Sci · 2013 Lymphoma is one of the most common malignant tumors in canine. Chemotherapy results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as a tumor suppressor and play ... Full text Link to item Cite

Apolipoproteins and apolipoprotein mimetic peptides modulate phagocyte trafficking through chemotactic activity.

Journal Article J Biol Chem · December 21, 2012 The plasma lipoprotein-associated apolipoproteins (apo) A-I and apoE have well described anti-inflammatory actions in the cardiovascular system, and mimetic peptides that retain these properties have been designed as therapeutics. The anti-inflammatory mec ... Full text Link to item Cite

Nitric oxide-mediated regulation of β-amyloid clearance via alterations of MMP-9/TIMP-1.

Journal Article J Neurochem · December 2012 Fibrillar amyloid plaques are largely composed of amyloid-beta (Aβ) peptides that are metabolized into products, including Aβ1-16, by proteases including matrix metalloproteinase 9 (MMP-9). The balance between production and degradation of Aβ proteins is c ... Full text Link to item Cite

Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis.

Journal Article BMC Gastroenterol · July 13, 2012 BACKGROUND: Intestinal mucositis is one of the major troublesome side effects of anticancer chemotherapy leading to poor patient compliance. In this study we addressed the role of the novel apolipoprotein E (ApoE) COG 133 mimetic peptide in 5-fluorouracil ... Full text Link to item Cite

The apoE-mimetic peptide, COG1410, improves functional recovery in a murine model of intracerebral hemorrhage.

Journal Article Neurocrit Care · April 2012 BACKGROUND: Apolipoprotein E has previously been demonstrated to modulate acute brain injury responses, and administration of COG1410, an apoE-mimetic peptide derived from the receptor-binding region of apoE, improves outcome in preclinical models of acute ... Full text Link to item Cite

Interaction between sex and apolipoprotein e genetic background in a murine model of intracerebral hemorrhage.

Journal Article Transl Stroke Res · March 2012 Emerging evidence suggests sex and apolipoprotein E (APOE) genotype separately modify outcomes after intracerebral hemorrhage (ICH). We test the hypothesis that an interaction exists between sex and APOE polymorphism in modifying outcomes after ICH and is ... Full text Link to item Cite

The potential role of presenilin 1 in regulation of synaptic function

Journal Article Cell and Tissue Biology · February 1, 2012 One of the earliest neuropathological symptoms of Alzheimer's disease is the loss of synapses that precedes the formation of amyloid plaques and neurodegeneration. Although most cases of early-onset familial Alzheimer's disease are caused by mutations in t ... Full text Cite

APOE-mimetic peptides reduce behavioral deficits, plaques and tangles in Alzheimer's disease transgenics.

Journal Article Neurodegener Dis · 2012 BACKGROUND: After age, the second largest risk factor for Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype, where APOE4 is associated with lower apoE protein levels, more severer brain pathology, enhanced inflammation and disease. Small peptide ... Full text Link to item Cite

Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.

Journal Article J Alzheimers Dis · 2012 Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where the ε4 allele increases and the ε2 allele decreases the risk for developing disease. Specific mutations within the amyloid-β ... Full text Link to item Cite

Apolipoprotein mimetic peptides: a new approach for the treatment of asthma.

Journal Article Front Pharmacol · 2012 New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM)-induced asthma to identify steroid-unresponsive genes that mig ... Full text Link to item Cite

A Novel SET Antagonist (OP449) Is Cytotoxic to CML Cells, Including the Highly-Resistant BCR-ABLT315I Mutant, and Demonstrates Enhanced Efficacy in Combination with ABL Tyrosine Kinase Inhibitors,

Conference Blood · November 18, 2011 AbstractAbstract 3757Background:The majority of patients with chronic myeloid leukemia (CML) achieve ... Full text Cite

Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer.

Journal Article Trends Pharmacol Sci · November 2011 Basal-like breast cancer is an aggressive disease with limited therapeutic options because these tumors frequently express the 'triple-negative' phenotype. We have recently reported that inducible nitric oxide synthase (NOS2) is a strong predictor of survi ... Full text Link to item Cite

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.

Journal Article Blood · October 13, 2011 B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells an ... Full text Link to item Cite

Targeting SET/I(2)PP2A oncoprotein functions as a multi-pathway strategy for cancer therapy.

Journal Article Oncogene · June 2, 2011 The SET oncoprotein participates in cancer progression by affecting multiple cellular processes, inhibiting the tumor suppressor protein phosphatase 2A (PP2A), and inhibiting the metastasis suppressor nm23-H1. On the basis of these multiple activities, we ... Full text Link to item Cite

Nitric oxide and redox mechanisms in the immune response.

Journal Article J Leukoc Biol · June 2011 The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppr ... Full text Link to item Cite

Abstract 615: PP2A activation as a strategy for treatment of breast cancer

Journal Article Cancer Research · April 15, 2011 AbstractBackground: Cells respond to stimuli by activating kinase signaling cascades that are counterbalanced by specific phosphatases so that the cell can return to a resting state. PP2A is a critical cellu ... Full text Cite

Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A.

Journal Article J Immunol · February 15, 2011 The molecular mechanism by which apolipoprotein E (apoE) suppresses inflammatory cytokine and NO production is unknown. Using an affinity purification approach, we found that peptide mimetics of apoE, derived from its receptor binding domain residues 130-1 ... Full text Link to item Cite

The apolipoprotein E-mimetic peptide COG112 inhibits NF-kappaB signaling, proinflammatory cytokine expression, and disease activity in murine models of colitis.

Journal Article J Biol Chem · February 4, 2011 Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a source of substantial morbidity and remains difficult to treat. New strategies for beneficial anti-inflammatory therapies would be highly desirable. Apolipoprotein ... Full text Link to item Cite

Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.

Journal Article J Neurosci · February 2, 2011 Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robus ... Full text Link to item Cite

[Potential role of presenilin 1 in regulation of synaptic function].

Journal Article Tsitologiia · 2011 One of the earliest neuropathological symptoms of Alzheimer's disease is the loss of synapses, which preceed the formation of amyloidosis and neurodegeneration. Although most cases of early-onset familial Alzheimer's disease are caused by mutations in the ... Link to item Cite

COG1410, an apolipoprotein E-based peptide, improves cognitive performance and reduces cortical loss following moderate fluid percussion injury in the rat.

Journal Article Behav Brain Res · December 25, 2010 COG1410, a small, novel ApoE-mimetic peptide derived from the receptor binding region of apolipoprotein E (ApoE), has been classified as anti-inflammatory in nature and improves motor, sensorimotor, and cognitive dysfunction following cortical contusion in ... Full text Link to item Cite

Familial Alzheimer's disease mutations in the presenilin 1 gene reduce cell-cell adhesion in transfected fibroblasts

Journal Article Biophysics · December 1, 2010 Experimental evidence has been obtained that mutations in the presenilin 1 (PS1) gene in familial Alzheimer's disease can lead to the disturbance of cell adhesion in model cell cultures. It was shown that, in L fibroblasts of mice with stable expression of ... Full text Cite

Traumatic brain injury exacerbates neurodegenerative pathology: improvement with an apolipoprotein E-based therapeutic.

Journal Article J Neurotrauma · November 2010 Cognitive impairment is common following traumatic brain injury (TBI), and neuroinflammatory mechanisms may predispose to the development of neurodegenerative disease. Apolipoprotein E (apoE) polymorphisms modify neuroinflammatory responses, and influence ... Full text Open Access Link to item Cite

Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease.

Journal Article Neuroscience · August 11, 2010 A central issue in the pathogenesis of tauopathy is the question of how tau protein dysfunction leads to neurodegeneration. We have previously demonstrated that the absence of tau protein is associated with destabilization of microtubules and impaired neur ... Full text Link to item Cite

An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.

Journal Article J Pharmacol Exp Ther · July 2010 Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRL ... Full text Link to item Cite

Tau deficiency leads to the upregulation of BAF-57, a protein involved in neuron-specific gene repression.

Journal Article FEBS Lett · June 3, 2010 Although tau is mainly located in the cell cytoplasm, mostly bound to tubulin, it may also be found in the nucleus of neurons. Hence, we tested whether tau might play a role in regulating the expression of certain genes by comparing gene expression in mice ... Full text Link to item Cite

Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits.

Journal Article Neurobiol Dis · March 2010 It has been proposed that deregulation of neuronal glycogen synthase kinase 3 (GSK3) activity may be a key feature in Alzheimer disease pathogenesis. We have previously generated transgenic mice that overexpress GSK3beta in forebrain regions including dent ... Full text Link to item Cite

[Familial Alzheimer's disease mutations in the presenilin 1 gene reduce cell-cell adhesion in transfected fibroblasts].

Journal Article Biofizika · 2010 Experimental evidence has been obtained that mutations in the presenilin 1 (PS1) gene in familial Alzheimer's disease can lead to the disturbance of cell adhesion in model cell cultures. It was shown that, in L fibroblasts of mice with stable expression of ... Link to item Cite

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

Journal Article PLoS One · December 7, 2009 BACKGROUND: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the ... Full text Link to item Cite

The SET Oncogene, a Potent PP2A Inhibitor, Is Elevated in CLL and Antagonism of SET Induces Apoptosis.

Conference Blood · November 20, 2009 AbstractAbstract 802Background and Significance:Even though we have treatments for CLL, it remains an ... Full text Cite

p53-dependent control of transactivation of the Pen2 promoter by presenilins.

Journal Article J Cell Sci · November 1, 2009 The senile plaques found in the brains of patients with Alzheimer's disease are mainly due to the accumulation of amyloid beta-peptides (A beta) that are liberated by gamma-secretase, a high molecular weight complex including presenilins, PEN-2, APH-1 and ... Full text Link to item Cite

Dithiolethione compounds inhibit Akt signaling in human breast and lung cancer cells by increasing PP2A activity.

Journal Article Oncogene · October 29, 2009 The chemopreventative effects of dithiolethione compounds are attributed to their activation of antioxidant response elements (AREs) by reacting with the Nrf2/Keap1 protein complex. In this study, we show antiproliferative effects of the dithiolethione com ... Full text Link to item Cite

Function of tau protein in adult newborn neurons.

Journal Article FEBS Lett · September 17, 2009 Levels of tau phosphorylation are high during the developmental period of intense neurite outgrowth, but decrease later. We here investigated whether tau protein plays a role in adult neurogenesis. First we demonstrate that new neurons generated in the sub ... Full text Link to item Cite

APOE genotype-specific differences in the innate immune response.

Journal Article Neurobiol Aging · September 2009 Apolipoprotein-E protein is an endogenous immunomodulatory agent that affects both the innate and the adaptive immune responses. Since individuals with the APOE4 gene demonstrate worsened pathology and poorer outcomes in many neurological disorders, we exa ... Full text Link to item Cite

Amyloid reduction by amyloid-beta vaccination also reduces mouse tau pathology and protects from neuron loss in two mouse models of Alzheimer's disease.

Journal Article J Neurosci · June 24, 2009 Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). Due to limitations in available animal models, however, it has been unclea ... Full text Link to item Cite

Tau--an inhibitor of deacetylase HDAC6 function.

Journal Article J Neurochem · June 2009 Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau patho ... Full text Link to item Cite

Protein transduction domain peptide mediates delivery to the brain via the blood-brain barrier in Drosophila melanogaster

Journal Article Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry · June 1, 2009 The phenomenon of protein transduction represents internalization of short peptides known as protein transduction domains (PTD) by cells. It is widely used in the development of new preparations for treatment of various brain disorders. However, the drug d ... Full text Cite

Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease.

Journal Article Neuroscience · March 31, 2009 The neurovascular unit (NVU) comprises cerebral blood vessels and surrounding astrocytes, neurons, perivascular microglia and pericytes. Astrocytes associated with the NVU are responsible for maintaining cerebral blood flow and ionic and osmotic balances i ... Full text Link to item Cite

COG1410, a novel apolipoprotein-E mimetic, improves functional and morphological recovery in a rat model of focal brain ischemia.

Journal Article J Neurosci Res · February 15, 2009 Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury with known neuroprotective effects exerted through antioxidant, antiinflammatory, antiexcitotoxic, and neurotrophic mechanisms. We have previously demonstr ... Full text Link to item Cite

Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.

Journal Article Stroke · February 2009 BACKGROUND AND PURPOSE: The purpose of the study was to evaluate the effect of APOE genotype and the feasibility of administering an apolipoprotein E-mimetic therapeutic to modify outcomes in a murine model of intracerebral hemorrhage. METHODS: Intracerebr ... Full text Link to item Cite

APOE genotype affects outcome in a murine model of sepsis: implications for a new treatment strategy.

Journal Article Anaesth Intensive Care · January 2009 In this study, we assessed whether apolipoprotein E (APOE) polymorphism affects inflammatory responses and mortality in the caecal ligation and puncture model of peritonitis. In addition, we determined the effects of APOE mimetic peptide administration in ... Full text Link to item Cite

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic drosophila model of Alzheimer's disease

Journal Article PLoS ONE · 2009 Background: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-b-protein (Ab). While Ab has been implicated in the causation of AD, the exact rol ... Full text Cite

[Protein transduction domain peptide mediates delivery to the brain via the blood-brain barrier in Drosophila].

Journal Article Biomed Khim · 2009 Protein transduction domain (PTD)-peptides greatly facilitate the delivery of high molecular weight macromolecules across the blood-brain barrier (BBB). This BBB-transport function is highly desirable and helps to enable the development of new therapeutics ... Link to item Cite

[Studying pathogenesis of Alzheimer's disease in a Drosophila melanogaster model: human APP overexpression in the brain of transgenic flies leads to deficit of the synaptic protein synaptotagmin].

Journal Article Genetika · January 2009 Alzheimer's disease (AD) is a progressive neurodegenerative disease whose main pathomorphological sign is synapse degeneration in the cortex and hippocampus. Abnormal synaptogenesis precedes amyloidosis and neurodegeneration and correlates with memory impa ... Link to item Cite

COG1410 improves cognitive performance and reduces cortical neuronal loss in the traumatically injured brain.

Journal Article J Neurotrauma · January 2009 We have previously shown that a single dose of COG1410, a small molecule ApoE-mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region, improves sensorimotor and motor outcome following cortical contusion injury (CCI). The present s ... Full text Link to item Cite

Studying the pathogenesis of Alzheimer's disease in a Drosophila melanogaster model: Human APP overexpression in the brain of transgenic flies leads to deficit of the synaptic protein synaptotagmin

Journal Article Russian Journal of Genetics · January 1, 2009 Alzheimer's disease (AD) is a progressive neurodegenerative disease whose main pathomorphological sign is synapse degeneration in the cortex and hippocampus. Abnormal synaptogenesis precedes amyloidosis and neurodegeneration and correlates with memory impa ... Full text Cite

Presenilin 1 mediates cell-cell adhesion in transfected L-fibroblasts

Conference NEW TRENDS IN ALZHEIMER AND PARKINSON RELATED DISORDERS: ADPD 2009 · January 1, 2009 Link to item Cite

The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.

Journal Article Neurobiol Aging · December 2008 The apolipoprotein E4 (APOE4) gene is a well-known risk factor for Alzheimer's disease (AD) and other neurological disorders. Post-menopausal women with AD who express at least one APOE4 gene have more severe neuropathology and worsened cognitive scores th ... Full text Link to item Cite

The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP.

Journal Article J Alzheimers Dis · December 2008 Nitric oxide synthase 2 (NOS2) and its gene product, inducible NOS (iNOS) play an important role in neuroinflammation by generating nitric oxide (NO), a critical signaling and redox factor in the brain. Although NO is associated with tissue damage, it can ... Full text Link to item Cite

Degeneration of growth cones in a culture of embryonic neurons of mouse with presenilin 1 knockout

Journal Article Biophysics · December 1, 2008 A comparative study of growth cone morphology in cultured embryonic neurons derived from wild type PS1(+/+) and knockout PS1(-/-) mice has been performed. Growth cones from wild type PS1(+/+) mice were well spread and usually formed radially continuous and ... Full text Cite

The apolipoprotein E-mimetic peptide COG112 inhibits the inflammatory response to Citrobacter rodentium in colonic epithelial cells by preventing NF-kappaB activation.

Journal Article J Biol Chem · June 13, 2008 Inflammatory bowel disease arises from the interplay between luminal bacteria and the colonic mucosa. Targeted inhibition of pro-inflammatory pathways without global immunosuppression is highly desirable. Apolipoprotein (apo) E has immunomodulatory effects ... Full text Link to item Cite

Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.

Journal Article J Neurosci · May 14, 2008 Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA). Specific mutations within the amyloid-beta protein (Abeta) peptide have been identified that cause familial forms of CAA. However, ... Full text Link to item Cite

Effects of FGF-2 overexpression in the Dutch/Iowa APP Transgenic mouse

Conference JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY · May 1, 2008 Link to item Cite

Apolipoprotein E4 genotype influences RAGE and LRP-1 expression

Conference JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY · May 1, 2008 Link to item Cite

Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype.

Journal Article Stroke · March 2008 BACKGROUND AND PURPOSE: We examined the associations among the vascular beta-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD). METHODS: ... Full text Link to item Cite

Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2.

Journal Article J Neurosci · February 13, 2008 Alzheimer's disease (AD) is characterized by three primary pathologies in the brain: amyloid plaques, neurofibrillary tangles, and neuron loss. Mouse models have been useful for studying components of AD but are limited in their ability to fully recapitula ... Full text Link to item Cite

[Degeneration of growth cones in a culture of embryonic neurons of mouse with presenilin 1 gene knockout].

Journal Article Biofizika · 2008 A comparative study of growth cone morphology in cultured embryonic neurons derived from wild type PS 1(+/+) and knockout PS 1(-/-) mice has been performed. Growth cones from wild type PS 1(+/+) mice were well spread and usually formed radially continuous ... Link to item Cite

Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways.

Journal Article Proc Natl Acad Sci U S A · October 23, 2007 Matrix metalloproteinases (MMPs) are of central importance in the proteolytic remodeling of matrix and the generation of biologically active molecules. MMPs are distinguished by a conserved catalytic domain containing a zinc ion, as well as a prodomain tha ... Full text Link to item Cite

Reelin signals survival through Src-family kinases that inactivate BAD activity.

Journal Article J Neurochem · October 2007 Reelin plays an important role in the migration of embryonic neurons, but its continuing presence suggests additional functions in the brain. We now report a novel function where reelin protects P19 embryonal cells from apoptosis during retinoic acid-induc ... Full text Link to item Cite

The tau N279K exon 10 splicing mutation recapitulates frontotemporal dementia and parkinsonism linked to chromosome 17 tauopathy in a mouse model.

Journal Article J Neurosci · August 22, 2007 Intracellular tau deposits are characteristic of several neurodegenerative disorders called tauopathies. The tau protein regulates the stability and assembly of microtubules by binding to microtubules through three or four microtubule-binding repeats (3R a ... Full text Link to item Cite

Apolipoprotein E and neurological disease: therapeutic potential and pharmacogenomic interactions.

Journal Article Pharmacogenomics · August 2007 The apolipoprotein E (apoE) polymorphism is emerging as a uniquely important genetic modifier that affects functional outcome from both acute and chronic neurological injuries. Recent attention has focused on common denominator mechanisms by which apoE mig ... Full text Link to item Cite

NOS2 in chronic neurodegeneration: Protection not damage

Conference JOURNAL OF NEUROCHEMISTRY · August 1, 2007 Link to item Cite

Microvascular injury and blood-brain barrier leakage in Alzheimer's disease.

Journal Article Neurobiol Aging · July 2007 Thinning and discontinuities within the vascular basement membrane (VBM) are associated with leakage of the plasma protein prothrombin across the blood-brain barrier (BBB) in Alzheimer's disease (AD). Prothrombin immunohistochemistry and ELISA assays were ... Full text Link to item Cite

Androgen-mediated immune function is altered by the apolipoprotein E gene.

Journal Article Endocrinology · July 2007 Androgens, like estrogens, have been linked to neuroprotective effects in the brain and to the improvement of cognitive function. Part of this effect may be due to the action of androgens on the innate immune response. We have examined the action of dihydr ... Full text Link to item Cite

COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.

Journal Article J Neurotrauma · July 2007 Traumatic brain injury (TBI) is a silent epidemic affecting approximately 1.4 million Americans annually, at an estimated annual cost of $60 billion in the United States alone. Despite an increased understanding of the pathophysiology of closed head injury ... Full text Link to item Cite

The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury.

Journal Article J Neurotrauma · July 2007 It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury. The present study evaluated the preclinical efficacy o ... Full text Link to item Cite

An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction.

Journal Article Neuroscience · February 23, 2007 Apolipoprotein E (apoE) modifies glial activation and the CNS inflammatory response in an isoform-specific manner. Peptides derived from the receptor-binding region of apoE have been demonstrated to maintain the functional activity of the intact protein, a ... Full text Link to item Cite

Presenilin 1 expression on the cell surface in motile polarized cells

Journal Article Biophysics · October 1, 2006 Most cases of early-onset familial Alzheimer's disease are caused by mutations in the presenilin 1 gene. Nonetheless, the function of presenilin 1 are not yet completely understood. It was shown that endogenous presenilin 1, as well as the adhesion protein ... Full text Cite

Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD.

Journal Article J Neuroinflammation · September 27, 2006 BACKGROUND: Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) o ... Full text Link to item Cite

Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage.

Journal Article Neurosurg Focus · September 15, 2006 OBJECT: The efficacy of nimodipine was examined in a murine model of subarachnoid hemorrhage (SAH). End points included the diameter of the lumen of the middle cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)-mimetic peptide, acetyl ... Full text Link to item Cite

Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis.

Journal Article J Pharmacol Exp Ther · September 2006 Apolipoprotein E (apoE), well known to play a role in lipid transport and cholesterol metabolism, also exerts anti-inflammatory and neuroprotective effects in the central nervous system. Recent clinical and genetic studies display an association between ap ... Full text Link to item Cite

NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease.

Journal Article Proc Natl Acad Sci U S A · August 22, 2006 Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelatio ... Full text Link to item Cite

Role of MAP1B in axonal retrograde transport of mitochondria.

Journal Article Biochem J · July 1, 2006 The MAPs (microtubule-associated proteins) MAP1B and tau are well known for binding to microtubules and stabilizing these structures. An additional role for MAPs has emerged recently where they appear to participate in the regulation of transport of cargos ... Full text Link to item Cite

Characterization of NO and cytokine production in immune-activated microglia and peritoneal macrophages derived from a mouse model expressing the human NOS2 gene on a mouse NOS2 knockout background.

Journal Article Antioxid Redox Signal · 2006 Significant differences exist in the production and release of nitric oxide (NO) from human macrophages versus macrophages of mouse origin. Human macrophages have been shown to respond poorly to stimuli that provoke strong inflammatory reactions from mouse ... Full text Link to item Cite

Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease.

Journal Article Acta Neurol Scand Suppl · 2006 The apolipoprotein E4 isoform (apoE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, and has also recently been associated with poor outcome after acute traumatic and ischemic brain injury. One mechanism by wh ... Full text Link to item Cite

A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage.

Journal Article Neurocrit Care · 2006 INTRODUCTION: Recent clinical observations demonstrate that the APOE4 genotype increases the development of delayed ischemic deficit and worsens prognosis following aneurysmal subarachnoid hemorrhage (SAH). In the current study, we use targeted replacement ... Full text Link to item Cite

[Expression of presenilin 1 on the cell surface in motile polarized cells].

Journal Article Biofizika · 2006 Most cases of familial early-onset Alzheimer's disease are caused by mutations in the presenilin 1 (PS1) gene. However, the cellular functions of PS1 are not yet completely understood. We showed that endogenous PS1 and the adhesion protein CD44 are redistr ... Link to item Cite

Selection of peptides binding to the amyloid b-protein reveals potential inhibitors of amyloid formation.

Journal Article Amyloid · December 2005 Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaques, cerebrovascular amyloid deposits, intracellular neurofibrillary tangles, and neuronal loss. Amyloid deposits are composed of insoluble fibers of a 39-4 ... Full text Link to item Cite

Reducing cerebral microvascular amyloid-beta protein deposition diminishes regional neuroinflammation in vasculotropic mutant amyloid precursor protein transgenic mice.

Journal Article J Neurosci · July 6, 2005 Cerebral microvascular amyloid-beta (Abeta) protein deposition is emerging as an important contributory factor to neuroinflammation and dementia in Alzheimer's disease and related familial cerebral amyloid angiopathy disorders. In particular, cerebral micr ... Full text Link to item Cite

Intrathecal administration of a novel apoE-derived therapeutic peptide improves outcome following perinatal hypoxic-ischemic injury.

Journal Article Neurosci Lett · June 24, 2005 Perinatal hypoxic-ischemic brain injury remains a significant clinical problem for which there remains no adequate therapeutic intervention. Apolipoprotein E (apoE) is a 299 amino acid protein that has been demonstrated to modify functional recovery follow ... Full text Link to item Cite

Sex steroids, APOE genotype and the innate immune system.

Journal Article Neurobiol Aging · March 2005 Microglia are a primary cellular component of the CNS innate immune system. Their response to conserved pathogen motifs is inherent and leads to the release of cytoactive factors that impact surrounding neurons and glia. The microglial response is modified ... Full text Link to item Cite

A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury.

Journal Article Exp Neurol · March 2005 Although apolipoprotein E4 (APOE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, the presence of the APOE4 allele is also associated with poor outcome after acute brain injury. One mechanism by which apoE may ... Full text Link to item Cite

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Journal Article J Neurosci · August 11, 2004 Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of ... Full text Link to item Cite

P3-183 Microvascular damage in Alzheimer's disease

Conference Neurobiology of Aging · July 2004 Full text Cite

Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.

Journal Article J Clin Invest · July 2004 Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Rec ... Full text Link to item Cite

Use of a multiple-enzyme/multiple-reagent assay system to quantify activity levels in samples containing mixtures of matrix metalloproteinases.

Journal Article Biochemistry · March 23, 2004 Matrix metalloproteinases (MMPs) are a family of enzymes that are up-regulated in many diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). Here we report on a novel technique that can be used to simultaneously measure activity levels for ... Full text Link to item Cite

Amyloidogenic and anti-amyloidogenic properties of recombinant transthyretin variants.

Journal Article Amyloid · March 2004 Most transthyretin (TTR) mutations lead to TTR amyloid depositions in patients with familial amyloidotic polyneuropathy and familial amyloidotic cardiomyopathy. However, though an amyloidogenic protein itself, TTR inhibits aggregation of Alzheimer's amyloi ... Full text Link to item Cite

Solution NMR studies of the A beta(1-40) and A beta(1-42) peptides establish that the Met35 oxidation state affects the mechanism of amyloid formation.

Journal Article J Am Chem Soc · February 25, 2004 The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of the 40-residue A beta(1-40) and 42-residue A beta(1-42) peptides into amyloid plaques. The structural changes associated with the conversion of monomeric A beta ... Full text Link to item Cite

APOE genotype-specific differences in human and mouse macrophage nitric oxide production.

Journal Article J Neuroimmunol · February 2004 Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a signif ... Full text Link to item Cite

Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical.

Journal Article Free Radic Biol Med · February 1, 2004 A growing body of evidence supports an important role for oxidative stress in the pathogenesis of Alzheimer's disease. Recently, a number of papers have shown a synergistic neurotoxicity of amyloid beta peptide and cupric ions. We hypothesized that complex ... Full text Link to item Cite

APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response.

Journal Article J Biol Chem · December 5, 2003 Human apolipoprotein E is the major apolipoprotein expressed in the brain and exists as three isoforms, designated E2, E3, and E4. Although evidence suggests that apolipoprotein E plays an important role in modifying systemic and brain inflammatory respons ... Full text Link to item Cite

A humanized NOS2 transgenic mouse

Conference FASEB JOURNAL · March 14, 2003 Link to item Cite

Apolipoprotein E and Reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-1/glycogen synthase kinase-3beta cascade.

Journal Article FASEB J · February 2003 Neurofibrillary tangles comprised of highly phosphorylated tau proteins are a key component of Alzheimer's disease pathology. Mice lacking Reelin (Reln), double-knockouts lacking the VLDL receptor (VLDLR) and ApoE receptor2 (ApoER2), and mice lacking disab ... Full text Link to item Cite

Effect of APOE genotype on microvascular basement membrane in Alzheimer's disease.

Journal Article J Neurol Sci · November 15, 2002 APOE4 homozygosity has been associated with an increased risk of sporadic Alzheimer's disease through a mechanism, which has yet to be defined. Recent evidence has suggested that microvascular basement membrane injury may be a critical factor in the pathog ... Full text Link to item Cite

Protein nitration is mediated by heme and free metals through Fenton-type chemistry: an alternative to the NO/O2- reaction.

Journal Article Proc Natl Acad Sci U S A · October 1, 2002 The chemical origins of nitrated tyrosine residues (NT) formed in proteins during a variety of pathophysiological conditions remain controversial. Although numerous studies have concluded that NT is a signature for peroxynitrite (ONOO(-)) formation, other ... Full text Link to item Cite

Transgenic mouse model for human oxidative stress in aging

Conference NEUROBIOLOGY OF AGING · July 1, 2002 Link to item Cite

Apolipoprotein E isoform mediated regulation of nitric oxide release.

Journal Article Free Radic Biol Med · June 1, 2002 Progressive dysfunction and death of neurons in Alzheimer's dementia is enhanced in patients carrying one or more APOE4 alleles who also display increased presence of oxidative stress markers. Modulation of oxidative stress is a nontraditional and physiolo ... Full text Link to item Cite

Apolipoprotein-E allele-specific regulation of nitric oxide production.

Journal Article Ann N Y Acad Sci · May 2002 Cognitive decline and dementia are key features of Alzheimer's disease (AD) that result from failure of neuronal function. Affected neurons demonstrate indices of nitrosative stress resulting from changes in nitric oxide (NO) mediated redox balance. Neurof ... Full text Link to item Cite

A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species.

Journal Article Ann N Y Acad Sci · May 2002 Nitric oxide (nitrogen monoxide, NO) plays a veritable cornucopia of regulatory roles in normal physiology. In contrast, NO has also been implicated in the etiology and sequela of numerous neurodegenerative diseases that involve reactive oxygen species (RO ... Full text Link to item Cite

Tau is essential to beta -amyloid-induced neurotoxicity.

Journal Article Proc Natl Acad Sci U S A · April 30, 2002 Senile plaques and neurofibrillary tangles, the two hallmark lesions of Alzheimer's disease, are the results of the pathological deposition of proteins normally present throughout the brain. Senile plaques are extracellular deposits of fibrillar beta-amylo ... Full text Link to item Cite

APOE and the regulation of microglial nitric oxide production: a link between genetic risk and oxidative stress.

Journal Article Neurobiol Aging · 2002 The mechanism linking the APOE4 gene with increased susceptibility for Alzheimer's disease (AD) and poorer outcomes following closed head injury and stroke is unknown. One potential link is activation of the innate immune system in the CNS. Our previously ... Full text Link to item Cite

Hypothermic treatment restores glucose regulated protein 78 (GRP78) expression in ischemic brain.

Journal Article Brain Res Mol Brain Res · November 1, 2001 Mild hypothermia is a well-known method of reducing brain damage caused by traumatic, hypoxic, and ischemic injury. To elucidate the neuroprotective mechanism induced by hypothermic treatment, we compared gene expression profiles in the hippocampus of gerb ... Full text Link to item Cite

Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine.

Journal Article Free Radic Biol Med · July 15, 2001 Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products a ... Full text Link to item Cite

Blood-brain barrier integrity in Alzheimer's disease.

Conference JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY · May 1, 2001 Link to item Cite

Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice

Journal Article Journal of Cell Science · April 23, 2001 Conflicting evidence supports a role for tau as an essential neuronal cytoskeletal protein or as a redundant protein whose function can be fulfilled by other microtubule-associated proteins. To investigate the function of tau in axonogenesis, we created ta ... Cite

Mechanisms of the antioxidant effects of nitric oxide.

Journal Article Antioxid Redox Signal · April 2001 The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components u ... Full text Link to item Cite

Activated cAMP-response element-binding protein regulates neuronal expression of presenilin-1.

Journal Article J Biol Chem · March 30, 2001 Upon binding to the cAMP-response element of a gene's promoter, the transcription factor known as cAMP-response element-binding protein (CREB) facilitates transcription of many different neuronal genes including those involved with synaptic function. Based ... Full text Link to item Cite

Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice.

Journal Article J Cell Sci · March 2001 Conflicting evidence supports a role for tau as an essential neuronal cytoskeletal protein or as a redundant protein whose function can be fulfilled by other microtubule-associated proteins. To investigate the function of tau in axonogenesis, we created ta ... Full text Link to item Cite

Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53.

Journal Article J Biol Chem · February 16, 2001 Survival factors suppress apoptosis by activating the serine/threonine kinase Akt. To investigate the molecular mechanism underlying activated Akt's ability to protect neurons from hypoxia or nitric oxide (NO) toxicity, we focused on the apoptosis-related ... Full text Link to item Cite

Apolipoprotein E acts to increase nitric oxide production in macrophages by stimulating arginine transport.

Journal Article Biochim Biophys Acta · February 14, 2001 Previous studies have shown that apolipoprotein E (apoE) plays a role in immune function by modulating tissue redox balance. Using a mouse macrophage cell line (RAW 264.7), we have examined the mechanism by which apoE regulates nitric oxide (NO) production ... Full text Link to item Cite

Apolipoprotein E4 stimulates cAMP response element-binding protein transcriptional activity through the extracellular signal-regulated kinase pathway.

Journal Article J Biol Chem · February 2, 2001 Inheritance of the epsilon4 allele of the apolipoprotein E gene (APOE4) is a major risk factor for the development of Alzheimer's disease (AD). Although the association between APOE4 and AD is well documented, the mechanism by which apolipoprotein E exerts ... Full text Link to item Cite

The role of Alzheimer's disease-related presenilin 1 in intercellular adhesion.

Journal Article Exp Cell Res · February 1, 2001 Most cases of familial early-onset Alzheimer's disease are caused by mutations in the presenilin 1 (PS1) gene. However, the cellular functions of PS1 are unknown. We showed predominant localization of PS1 to cell-cell contacts of the plasma membrane in hum ... Full text Link to item Cite

A pathway of neuronal apoptosis induced by hypoxia/reoxygenation: roles of nuclear factor-kappaB and Bcl-2.

Journal Article J Neurochem · August 2000 As a model of the reperfusion injury found in stroke, we have exposed neurons to hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation (H/R) respond by activating nuclear factor-kappaB (NFkappaB), releasing cytochrome c from their m ... Full text Link to item Cite

In vitro polymerization of tau protein monitored by laser light scattering: method and application to the study of FTDP-17 mutants.

Journal Article Biochemistry · May 23, 2000 Tau polymerization into the filaments that compose neurofibrillary tangles is seminal to the development of many neurodegenerative diseases. It is therefore important to understand the mechanisms involved in this process. However, a consensus method for mo ... Full text Link to item Cite

Expression of the apolipoprotein E gene does not affect motor recovery after sensorimotor cortex injury in the mouse.

Journal Article Neuroscience · 2000 Motor recovery after unilateral sensorimotor cortex ablation or sham-injury was measured in apolipoprotein E knockout and wild-type mice by testing their abilities to traverse a narrow beam. All mice trained without difficulty. Sham-operated mice performed ... Full text Link to item Cite

Microglial contribution to oxidative stress in Alzheimer's disease.

Journal Article Ann N Y Acad Sci · 2000 Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia ... Full text Link to item Cite

Mechanisms of cell death governed by the balance between nitrosative and oxidative stress.

Journal Article Ann N Y Acad Sci · 2000 Many cellular functions in physiology are regulated by the direct interaction of NO with target biomolecules. In many pathophysiologic and toxicologic mechanisms, NO first reacts with oxygen, superoxide or other nitrogen oxides to subsequently elicit indir ... Full text Link to item Cite

Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix.

Journal Article Proc Natl Acad Sci U S A · July 6, 1999 Most familial early-onset Alzheimer's disease cases are caused by mutations in the presenilin 1 (PS1) gene. Subcellular localization of the endogenous PS1 is essential for understanding its function, interactions with proteins, and role in Alzheimer's dise ... Full text Link to item Cite

Amyloid beta peptides do not form peptide-derived free radicals spontaneously, but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides.

Journal Article J Biol Chem · April 2, 1999 Amyloid beta (Abeta) peptides play an important role in the pathogenesis of Alzheimer's disease. Free radical generation by Abeta peptides was suggested to be a key mechanism of their neurotoxicity. Reports that neurotoxic free radicals derived from Abeta- ... Full text Link to item Cite

Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.

Journal Article Biochem Biophys Res Commun · November 17, 1997 Induction of oxidative stress has been implicated as a causative factor in chronic neurodegenerative diseases such as Alzheimer's disease. Apolipoprotein-E (apoE) and amyloid-beta peptide (A beta) have been reported to alter the redox state of the brain. U ... Full text Link to item Cite

Transcriptional regulation of the mouse presenilin-1 gene.

Journal Article J Biol Chem · September 19, 1997 The presenilin-1 (PS-1) gene encodes at least three separate mRNA transcripts from its 12 exons, which are spread over 50 kilobase pairs of mouse DNA. The first transcript begins with exon 1A, whereas the other transcripts begin with exon 1B. Different por ... Full text Link to item Cite

Is amyloid beta-protein glycated in Alzheimer's disease?

Journal Article Neuroreport · March 3, 1997 Recent data suggest that protein glycation is involved in the process of amyloid formation in Alzheimer's disease (AD). To further investigate this issue, we analyzed the presence of advanced glycation end products (AGE) in soluble and insoluble forms of a ... Full text Link to item Cite

Radical changes in beta-amyloid form and function.

Journal Article Mol Chem Neuropathol · 1996 A growing body of evidence supports the nucleation hypothesis of fibrillar amyloid formation. In this article, it is hypothesized that the fibrils formed with human A beta, rodent A beta, and a mixture of the two peptides may form nearly identical physical ... Full text Link to item Cite

Neuroinflammatory mechanisms in Alzheimer's disease: New opportunities for drug discovery

Journal Article Expert Opinion on Investigational Drugs · January 1, 1996 Full text Cite

Early AGEing and Alzheimer's.

Journal Article Nature · March 23, 1995 Full text Link to item Cite

Advanced glycosylation end-products contribute to amyloidosis in Alzheimer's disease

Conference RESEARCH ADVANCES IN ALZHEIMER'S DISEASE AND RELATED DISORDERS · January 1, 1995 Link to item Cite

Transthyretin sequesters amyloid beta protein and prevents amyloid formation.

Journal Article Proc Natl Acad Sci U S A · August 30, 1994 The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patien ... Full text Link to item Cite

Advanced glycation end products contribute to amyloidosis in Alzheimer disease.

Journal Article Proc Natl Acad Sci U S A · May 24, 1994 Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino-acid beta-amyloid peptide (beta AP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic ... Full text Link to item Cite

The release of Alzheimer's disease beta amyloid peptide is reduced by phorbol treatment.

Journal Article J Biol Chem · March 18, 1994 Amyloid precursor protein (APP) is cleaved predominantly within the beta amyloid peptide (BAP) domain to release a non-amyloidogenic amino-terminal PN2 fragment. Treatment of cells with phorbol dibutyrate, an agent which activates protein kinase C, has bee ... Link to item Cite

Enzymatic generation of the amino terminus of the beta-amyloid peptide.

Journal Article J Biol Chem · August 5, 1993 The major pathological change in Alzheimer's disease is the deposition of 39-42-amino acid beta-amyloid peptide (BAP) in the brain. Since BAP begins at the aspartate residue (Asp1, or codon 672 of the amyloid precursor protein (APP)770 transcript), the abi ... Link to item Cite

Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells.

Journal Article J Biol Chem · December 15, 1992 Abnormal proteolytic processing of amyloid precursor protein (APP) is thought to be central to the formation and deposition of beta amyloid peptide in Alzheimer's disease. A putative "secretase" activity normally releases an amino-terminal APP fragment by ... Link to item Cite

Altered genetic response to beta-adrenergic receptor activation in late passage C6 glioma cells.

Journal Article J Neurosci Res · October 1992 Previous studies have demonstrated variability in the phenotype of rat C6 glioma cells. In the present study, we compared morphology, growth rate, and beta-adrenergic regulation of gene expression in early (P39-47) and late (P55-90) passage C6 cells. Morph ... Full text Link to item Cite

Interleukin-1 beta decreases acetylcholine measured by microdialysis in the hippocampus of freely moving rats.

Journal Article Brain Res · June 7, 1991 Interleukin (IL-1) is a cytokine which plays an important role in the modulation of the acute response in host defense. This cytokine is also increased in patients with Alzheimer's disease. In the present experiment systemic injection of IL-1 beta (7.5-50 ... Full text Link to item Cite

Quantitative measurement of alternatively spliced amyloid precursor protein mRNA expression in Alzheimer's disease and normal brain by S1 nuclease protection analysis.

Journal Article Neurobiol Aging · 1991 We have used an S1 nuclease protection strategy to measure alternatively spliced amyloid precursor protein (APP) mRNAs associated with Alzheimer's disease (AD) to determine whether the expression of either one or more of the transcripts correlate with obse ... Full text Link to item Cite

A novel species-specific RNA related to alternatively spliced amyloid precursor protein mRNAs.

Journal Article Neurobiol Aging · 1991 Using an S1 nuclease protection assay, we have identified a novel "variant" Amyloid Precursor Protein (APP) RNA in human brain which is 3-6-fold more abundant than APP-770, but less abundant than APP-751 or APP-695. This variant, referred to as amyloid pre ... Full text Link to item Cite

Interleukin-1 stimulates the beta-amyloid precursor protein promoter.

Journal Article Cell Mol Neurobiol · December 1990 1. Amyloid plaques found in the brains of Alzheimer's diseased patients are composed of the 42 amino acid beta-amyloid peptide (BAP) which is processed out of the larger amyloid precursor protein (APP). 2. To study the regulation of the APP gene expression ... Full text Link to item Cite

Differential expression of gamma-aminobutyric acidA receptor subunits.

Journal Article Mol Pharmacol · May 1990 A 1.8-kilobase (kb) cDNA clone for a beta 1 subunit of the human gamma-aminobutyric acidA (GABAA) receptor has been isolated and sequenced. The longest open reading frame of the clone, pCLL610, contains nucleotide sequence encoding a portion of the putativ ... Link to item Cite

Effects of continuous diazepam administration on GABAA subunit mRNA in rat brain.

Journal Article J Mol Neurosci · 1990 Rats treated chronically with diazepam develop tolerance to diazepam effects and show changes in sensitivity of GABAergic systems. In order to investigate possible molecular mechanisms associated with these changes, we have evaluated the effects of acute a ... Full text Link to item Cite

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

Journal Article Proc Natl Acad Sci U S A · October 1989 We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of th ... Full text Link to item Cite

Isolation and expression of multiple forms of beta amyloid protein precursor cDNAs.

Journal Article Prog Clin Biol Res · 1989 Alzheimer's disease (AD) is associated with the extra-normal accumulation of a 42 amino acid (aa) beta-amyloid peptide (BAP) in amyloid plaques and cerebrovascular deposits. Though BAP is deposited exclusively in brains of AD and Down syndrome patients, th ... Link to item Cite

Increasing amyloid peptide precursor production and its impact on Alzheimer's disease.

Journal Article Neurobiol Aging · 1989 Amyloid peptide precursor (APP) gene expression increases in the brains of patients with Alzheimer's disease (AD). Regulation of expression at the transcriptional and posttranscriptional levels contributes significantly to these increases. Polypeptide horm ... Full text Link to item Cite

Focusing on IL-1-promotion of beta-amyloid precursor protein synthesis as an early event in Alzheimer's disease.

Journal Article Neurobiol Aging · 1989 A rationale for increased synthesis of beta-amyloid peptide percursor (APP) protein in Alzheimer's disease (AD) is developed in which Interleukin-1 (IL-1) plays a key role. This cytokine is elevated in AD, its receptors are on APP mRNA positive cells and i ... Full text Link to item Cite

Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor.

Journal Article Biochem Biophys Res Commun · October 31, 1988 A cDNA clone of an alpha subunit of the human GABA-A receptor has been isolated. The human clone (pCLL800) contains 1055 nucleotides in an open reading frame and 260 nucleotides in the 5' non-coding region. The 351 amino acid sequence of this human alpha s ... Full text Link to item Cite

Absence of mutation in the beta-amyloid cDNAs cloned from the brains of three patients with sporadic Alzheimer's disease.

Journal Article Brain Res · September 1988 Using an oligonucleotide probe, we isolated cDNA clones corresponding to the precursor of the beta-amyloid peptide (BAP) from brain libraries of 3 patients with sporadic Alzheimer's disease (AD). DNA sequencing showed that the largest cDNA clone encompasse ... Full text Link to item Cite

Multiple forms of beta-amyloid peptide precursor RNAs in a single cell type.

Journal Article Neurobiol Aging · 1988 The longest open reading frames (ORFs) of three different cDNAs ([10, 12, 18, 26], and this report) contain the exact 42 amino acid (aa) sequence of the beta-amyloid peptide (BAP) which is selectively deposited in Alzheimer's diseased (AD) brains. Each of ... Full text Link to item Cite

Recombinant human interleukin 1 alpha: purification and biological characterization.

Journal Article J Immunol · April 1, 1986 Interleukin 1 (IL 1) is a polypeptide hormone produced by activated macrophages that affects many different cell types involved in immune and inflammatory responses. The cloning and expression of a murine IL 1 cDNA in Escherichia coli encoding a polypeptid ... Link to item Cite

Transcript length heterogeneity at the small heat shock protein genes of Drosophila.

Journal Article J Mol Biol · November 5, 1985 Expression of the small heat shock protein (hsp) genes can be induced in cultured Drosophila cells by high temperature shock and by exposure to physiological doses of the insect molting hormone ecdysterone. Northern blot analysis was performed in order to ... Full text Link to item Cite

Isolation of specific chromosomes and their DNA

Journal Article Gene Analysis Techniques · January 1, 1985 Chromosome 21 is the only human chromosome in the mouse human hybrid, WA17. WA17 cells were treated with 0.1 μg/ml Colcemid, lysed, and mitotic chromosomes were separated based on their sizes in sucrose velocity gradients. The position of chromosome 21 on ... Full text Cite

Steroid and high-temperature induction of the small heat-shock protein genes in Drosophila.

Journal Article J Mol Biol · September 15, 1984 Transcription of the four small heat-shock protein genes of Drosophila melanogaster can be induced in cultured cells by high-temperature shock, or by physiological doses of the moulting hormone, ecdysterone. We have characterized and compared the two induc ... Full text Link to item Cite

Stimulation of cytoplasmic actin gene transcription and translation in cultured Drosophila cells by ecdysterone.

Journal Article J Biol Chem · February 10, 1984 When cultured Drosophila line S3 cells are incubated in the presence of the steroid hormone, ecdysterone, they flatten, elongate, and become motile. We show here that accompanying this morphological transformation there is a 5-fold increase in the rate of ... Link to item Cite

PURIFICATION OF HUMAN CHROMOSOME-21

Conference JOURNAL OF CELL BIOLOGY · January 1, 1984 Link to item Cite

The isolation of ecdysterone inducible genes by hybridization subtraction chromatography.

Journal Article Nucleic Acids Res · March 11, 1981 We have developed a procedure for selectively enriching a mRNA population for inducible sequences. Other than the induced mRNA species, the population of mRNA in control cells is approximately the same as the mRNA population in induced cells. Cytoplasmic m ... Full text Link to item Cite