A5011049890- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Diet and metabolism studies
- Advanced Glycation End Products research
- Regulation of Appetite and Obesity
- Cholinesterase and Neurodegenerative Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Balance, Gait, and Falls Prevention
- Neurological Disease Mechanisms and Treatments
- Antioxidant Activity and Oxidative Stress
- Biochemical effects in animals
- Prenatal Screening and Diagnostics
- Cholesterol and Lipid Metabolism
- Sphingolipid Metabolism and Signaling
- HIV Research and Treatment
- Genetics, Aging, and Longevity in Model Organisms
- Nutritional Studies and Diet
- Drug Transport and Resistance Mechanisms
Pennington Biomedical Research Center
2016-2025
Louisiana State University
2008-2024
Federal Office of Public Health
2023
Louisiana State University System
2009-2019
University of Pittsburgh
2019
Albert Einstein College of Medicine
2018
University of Louisiana at Monroe
2016
University of Cincinnati Medical Center
2014
Allen Institute for Brain Science
2014
Mayfield Brain & Spine
2014
Oxidative stress is implicated in neuronal apoptosis that occurs physiological settings and neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, involved the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly role superoxide peroxynitrite apoptosis, we generated neural cell lines transgenic mice overexpress human manganese dismutase (MnSOD). In cultured pheochromocytoma PC6 cells,...
Abstract : Inhibition of proteasome activity is sufficient to induce neuron degeneration and death ; however, altered in a neurodegenerative disorder has not been demonstrated. In the present study, we analyzed short‐postmortem‐interval autopsied brains from 16 Alzheimer's disease (AD) nine age‐ sex‐matched controls. A significant decrease was observed hippocampus parahippocampal gyrus (48%), superior middle temporal gyri (38%), inferior parietal lobule (28%) AD patients compared with...
<b>Objective: </b> To determine if increased levels of oxidative damage are present in the brains persons with mild cognitive impairment (MCI), a condition that often precedes Alzheimer disease (AD). <b>Methods: The authors assessed amount protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and malondialdehyde superior middle temporal gyri (SMTG) cerebellum short postmortem interval longitudinally evaluated normal subjects those MCI early AD. <b>Results: Elevated carbonyls...
Glutamate transporters are involved in the maintenance of synaptic glutamate concentrations. Because its potential neurotoxicity, clearance from cleft may be critical for neuronal survival. Inhibition uptake synapse has been implicated several neurodegenerative disorders. In particular, is inhibited Alzheimer's disease (AD); however, mechanism decreased transporter activity unknown. Oxidative damage brain models neurodegeneration, as well AD. by oxidative reactive oxygen species and lipid...
Abstract: Deposits of amyloid β‐peptide (Aβ), reduced glucose uptake into brain cells, oxidative damage to cellular proteins and lipids, excitotoxic mechanisms have all been suggested play roles in the neurodegenerative process Alzheimer's disease. Synapse loss is closely correlated with cognitive impairments disease, suggesting that synapse may be site at which degenerative are initiated propagated. We report Aβ causes oxyradical‐mediated impairment transport, glutamate mitochondrial...
Alzheimer's disease (AD) is a progressive and devastating disorder that often preceded by mild cognitive impairment (MCI). In the present study, we report in multiple cortical areas of MCI AD subjects, there significant ribosome function not observed cerebellum same subjects. The associated with decreased rate capacity for protein synthesis, ribosomal RNA tRNA levels, increased oxidation. No alteration level initiation factors was brain regions exhibiting impairments synthesis. Together,...
J. Neurochem. (2012) 120 , 1060–1071. Abstract This study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that saturated acid palmitic acid, as well lauric and stearic trigger release TNFα IL‐6 from Unsaturated were unable to induce cytokine Furthermore, require Toll‐like receptor 4 rather than CD36 or 2, do not depend metabolism palmitoyl‐CoA. Inhibitor studies revealed pharmacologic inhibition p38 p42/44 MAPK pathways prevents...
J. Neurochem. (2010) 114 , 1581–1589. Abstract Long term consumption of a high fat diet (HFD) contributes to increased morbidity and mortality. Yet the specific effects HFD on brain aging are poorly understood. In present study 20‐month old male C57Bl/6 mice were fed either ‘western diet’ (41% fat), very lard (60% or corresponding control diets for 16 weeks then assessed changes in metabolism homeostasis. Although both HFDs adiposity fasting blood glucose, only age‐related oxidative damage...
Abstract We report increased modification of proteins by 4‐hydroxynoneal (HNE), a product membrane lipid peroxidation, in the lumbar spinal cord sporadic amyotrophic lateral sclerosis (ALS) patients versus that neurologically normal controls. By immunohistochemistry, HNE‐protein was detected ventral horn motor neurons, and immunoprecipitation analysis revealed one modified HNE astrocytic glutamate transporter EAAT2. Given function can be severely compromised as previously demonstrated for...
In the present study effects of 17β-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity age-related neurodegenerative diseases such as Alzheimer's disease, and estrogens have potent immunosuppressive properties outside brain. To determine role that cells might play in estrogen-mediated neuroprotection, primary rat microglia N9 cell lines were treated increasing doses before or during immunostimulation by...
Removal of extracellular glutamate at synapses, by specific high-affinity transporters, is critical to prevent excitotoxic injury neurons. Oxidative stress has been implicated in the pathogenesis an array prominent neurodegenerative conditions that involve degeneration synapses and neurons glutamatergic pathways including stroke, Alzheimer's, Parkinson's Huntington's diseases. Although cell culture data indicate oxidative insults can impair key membrane regulatory systems ion-motive ATPases...
Abstract: Alzheimer's disease (AD) is widely held to be a disorder associated with oxidative stress due, in part, the membrane action of amyloid β‐peptide (Aβ). Aβ‐associated free radicals cause lipid peroxidation, major product which 4‐hydroxy‐2‐ trans ‐nonenal (HNE). We determined whether HNE would alter conformation synaptosomal proteins, might related known neurotoxicity Aβ and HNE. Electron paramagnetic resonance spectroscopy, using protein‐specific spin label,...
Many cases of autosomal dominant early onset Alzheimer's disease (AD) result from mutations in the gene encoding presenilin-1 (PS-1). PS-1 is an integral membrane protein expressed ubiquitously neurons throughout brain which it located primarily endoplasmic reticulum (ER). Although pathogenic mechanism unknown, recent findings suggest that PS render vulnerable to apoptosis. Because increasing evidence indicates mitochondrial alterations contribute neuronal death AD, we tested hypothesis...