Journal ArticleJ 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 textLink to itemCite
Journal ArticlePharmaceutics · 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleFront 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 textOpen AccessLink to itemCite
Journal ArticleASN 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 textLink to itemCite
Journal ArticleEur 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 textLink to itemCite
Journal ArticleAlzheimers 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 textOpen AccessLink to itemCite
Journal ArticleTransl 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleEndocr 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 textLink to itemCite
Journal ArticleTransl 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleOncotarget · 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 textLink to itemCite
Journal ArticleOncotarget · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticlePharmaceutics · 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleFront 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 textOpen AccessLink to itemCite
Journal ArticleASN 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 textLink to itemCite
Journal ArticleEur 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 textLink to itemCite
Journal ArticleAlzheimers 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 textOpen AccessLink to itemCite
Journal ArticleTransl 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleEndocr 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 textLink to itemCite
Journal ArticleTransl 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleOncotarget · 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 textLink to itemCite
Journal ArticleOncotarget · 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 textLink to itemCite
Journal ArticleNeurosci 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleCancer 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 textOpen AccessCite
Journal ArticleSci 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 textOpen AccessLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textOpen AccessLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleClin 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 textLink to itemCite
Journal ArticlePLoS 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 textLink to itemCite
Journal ArticleBiochemistry (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 textCite
Journal ArticleBiomed 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 textLink to itemCite
ConferenceBlood · November 15, 2013
AbstractBackgroundThe SET oncoprotein, an inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia cells, preventi ...
Full textCite
ConferenceCancer 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 textCite
Journal ArticleJ 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 textOpen AccessLink to itemCite
Journal ArticleExp 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 textLink to itemCite
Journal ArticleNeurodegener 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBMC 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 textLink to itemCite
Journal ArticleNeurocrit 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 textLink to itemCite
Journal ArticleTransl 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 textLink to itemCite
Journal ArticleCell 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 textCite
Journal ArticleNeurodegener 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
ConferenceBlood · November 18, 2011
AbstractAbstract 3757Background:The majority of patients with chronic myeloid leukemia (CML) achieve ...
Full textCite
Journal ArticleTrends 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 textLink to itemCite
Journal ArticleBlood · 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 textLink to itemCite
Journal ArticleOncogene · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleCancer 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 textCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleTsitologiia · 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 itemCite
Journal ArticleBehav 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 textLink to itemCite
Journal ArticleBiophysics · 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 textCite
Journal ArticleJ 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 textOpen AccessLink to itemCite
Journal ArticleNeuroscience · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleFEBS 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleBiofizika · 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 itemCite
Journal ArticlePLoS 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 textLink to itemCite
ConferenceBlood · November 20, 2009
AbstractAbstract 802Background and Significance:Even though we have treatments for CLL, it remains an ...
Full textCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleOncogene · 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 textLink to itemCite
Journal ArticleFEBS 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiochemistry (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 textCite
Journal ArticleNeuroscience · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleStroke · 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 textLink to itemCite
Journal ArticleAnaesth 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 textLink to itemCite
Journal ArticlePLoS 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 textCite
Journal ArticleBiomed 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 itemCite
Journal ArticleGenetika · 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 itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleRussian 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 textCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiophysics · 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 textCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleStroke · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiofizika · 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 itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticlePharmacogenomics · 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleEndocrinology · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleNeuroscience · 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 textLink to itemCite
Journal ArticleBiophysics · 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 textCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleNeurosurg 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleBiochem 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 textLink to itemCite
Journal ArticleAntioxid 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 textLink to itemCite
Journal ArticleActa 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 textLink to itemCite
Journal ArticleNeurocrit 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 textLink to itemCite
Journal ArticleBiofizika · 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 itemCite
Journal ArticleAmyloid · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleNeurosci 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleExp 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiochemistry · 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 textLink to itemCite
Journal ArticleAmyloid · 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleFree 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleFASEB 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleFree 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleBrain 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 textLink to itemCite
Journal ArticleFree 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 textLink to itemCite
Journal ArticleJournal 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
Journal ArticleAntioxid 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiochim 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleExp 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiochemistry · 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 textLink to itemCite
Journal ArticleNeuroscience · 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleAnn 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBiochem 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleNeuroreport · 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleJ 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 itemCite
Journal ArticleJ 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 itemCite
Journal ArticleJ 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 itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleBrain 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleCell 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 textLink to itemCite
Journal ArticleMol 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 itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleProc 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 textLink to itemCite
Journal ArticleProg 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 itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleBiochem 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 textLink to itemCite
Journal ArticleBrain 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 textLink to itemCite
Journal ArticleNeurobiol 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 textLink to itemCite
Journal ArticleJ 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 itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleGene 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 textCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 itemCite
Journal ArticleNucleic 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 textLink to itemCite