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Search Results to Benjamin Wolozin, MD, PhD

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Research Expertise & Professional Interests Dr. Wolozin’s research examines the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. His laboratory is currently focused on the role of RNA binding proteins and translational regulation in disease processes. Parkinson’s disease: The research on Parkinson Disease focuses on genetic factors implicated in Parkinson’s disease, including LRRK2, a-synuclein, parkin, PINK1 and DJ-1. Research in our laboratory suggests that genetic mutations linked to Parkinson’s disease act by converging on a biological system that integrates the stress response, regulating autophagy, protein translation and mitochondrial function. Using genetically modified cells (e.g., primary neuronal cultures or cell lines) and genetically modified animals (C. elegans and mice), we have demonstrated that a-synuclein and LRRK2 enhance the sensitivity of dopaminergic neurons to mitochondrial dysfunction. Our work points to particular biochemical pathways mediating the actions of LRRK2. We have recently demonstrated that LRRK2 binds to MKK6, a kinase that lies upstream of p38 and regulates the stress response. LRRK2 regulates membrane localization of its binding proteins, including MKKs, JIPs, rac1 (a small GTPase) and other important proteins mediating the stress response. This work has direct relevance to therapy because it points to chemicals that might protect dopaminergic neurons and modify the course of Parkinson’s disease. For instance, we are investigating the action of SirT1 agonists (such resveratrol, the compound found in red wine or SRT1720, produced by Sirtris Pharmaceuticals), which stimulate synthesis of anti-oxidant enzymes and appear to offer protection in animal models of Parkinson’s disease. We are also investigating the action of brain penetrant analogues of rapamycin, which stimulate the neuron to remove protein aggregates, and offer neuroprotection through mechanisms complementary to SirT1. Amyotrophic Lateral Sclerosis (ALS): Our current work focuses on a protein, TDP-43, that was recently shown to be the predominant protein that accumulates during the course of the disease. We have shown that TDP-43 is a stress granule protein, and that TDP-43 pathology co-localizes with other stress granule markers in spinal cords of subjects with ALS, as well as those with Frontotemporal Dementia. We are currently examining how TDP-43 and disease-linked mutations in TDP-43 modify synaptic function in neuronal arbors. We are using protein binding assays (immunoprecipitation, mass spectrometry) and imaging assay (fixed cells and live cell imaging) to determine the effects of TDP-43 and its mutations. We use cell lines, primary cultures of hippocampal neurons and human brain samples for our studies. We also have an active drug discover program related to TDP-43. This program utilizes cells that inducibly over-express TDP-43, as well as lines of C. elegans expressing TDP-43 and studies in primary cultures of hippocampal neurons. We examine the compounds using imaging (in collaboration with Marcie Glicksman at LDDN) and biochemistry. Alzheimer disease (AD): We have recently extended our work on stress granules to Alzheimer’s disease. As with ALS, we have shown that tau pathology (neurofibrillary tangles) in the AD brain co-localizes with stress granule markers. The amount of stress granule pathology in the AD brain is very striking. Proteins such as TIA-1, G3BP and TTP, strongly accumulate. Interestingly, though, the pattern of accumulation differs based on the stress granule protein. The pathology appears to correlate with binding to tau protein. TIA-1 and TTP both bind to tau, while G3BP does not bind tau. Stress granules might also directly modulate tau pathology, because co-transfecting TIA-1 with tau induces formation of phosphorylated tau inclusions. The work on AD and stress granules uses biochemical/immunochemical studies focusing on proteins implicated in AD (e.g., antibodies to tau) and on stress granule markers. The work also uses extensive imaging assays (fixed cells, live cell imaging, confocal microscopy). We use studies of hippocampal neurons grown culture, transgenic mice expressing P301L tau and human tissues.
Self-Described Keywords Alzheimer's disease

One or more keywords matched the following items that are connected to Wolozin, Benjamin

Item TypeName
Concept Alzheimer Disease
Academic Article Protein alterations in olfactory neuroblasts from Alzheimer donors.
Academic Article Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation.
Academic Article Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3.
Academic Article Reductionist science and Alzheimer's disease: redoubling our effort in redox chemistry.
Academic Article Direct association of presenilin-1 with beta-catenin.
Academic Article Longitudinal stability of CSF tau levels in Alzheimer patients.
Academic Article Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors.
Academic Article A fluid connection: cholesterol and Abeta.
Academic Article Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion.
Academic Article Cyp46 (24S-cholesterol hydroxylase): a genetic risk factor for Alzheimer disease.
Academic Article Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.
Academic Article Cholesterol and Alzheimer's disease.
Academic Article Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology.
Academic Article Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients.
Academic Article The cellular biochemistry of cholesterol and statins: insights into the pathophysiology and therapy of Alzheimer's disease.
Academic Article Oxidative damage in the olfactory system in Alzheimer's disease.
Academic Article Cholesterol and the biology of Alzheimer's disease.
Academic Article Differential expression of cholesterol hydroxylases in Alzheimer's disease.
Academic Article Cholesterol, statins and dementia.
Academic Article Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty.
Academic Article The players on the gamma-secretase team.
Academic Article Re-assessing the relationship between cholesterol, statins and Alzheimer's disease.
Academic Article Interventions for heart disease and their effects on Alzheimer's disease.
Academic Article Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease.
Academic Article Leptin: a novel therapeutic strategy for Alzheimer's disease.
Academic Article Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later.
Academic Article Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis.
Academic Article Iatrogenic risk factors for Alzheimer's disease: surgery and anesthesia.
Academic Article Recent advances in the neurochemistry of Alzheimer's disease.
Academic Article Characterization of insulin degrading enzyme and other amyloid-ß degrading proteases in human serum: a role in Alzheimer's disease?
Academic Article TDP-43: a new player on the AD field?
Academic Article Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies.
Academic Article Statins and therapy of Alzheimer's disease: questions of efficacy versus trial design.
Academic Article Alz-50 antibody recognizes Alzheimer-related neuronal changes.
Academic Article Genes, Behaviour and Health
Academic Article Cholesterol and Alzheimer’s disease
Academic Article Response to Letter: Statin-Alzheimer Disease Association Not Yet Proven
Academic Article Looking beyond b-amyloid: a-Synuclein and Neurodegeneration
Academic Article Cholesterol, Statins and Alzheimer’s disease: Past, Present and Future
Academic Article Recent advances in the neurochemistry of Alzheimer's Disease
Academic Article Statins and therapy of Alzheimer's disease: questions of efficacy versus trial design
Academic Article Presenilins and their role in apoptosis
Academic Article Interpreting Clinical Studies of Putative Therapeutics for Alzheimer’s disease
Academic Article Immunochemical approaches to the diagnosis of Alzheimer's Disease
Academic Article Development of neuropathology similar to Alzheimer's Disease in transgenic mice overexpressing the 717V-F b-amyloid precursor protein
Academic Article Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease.
Academic Article A neuronal antigen in the brains of Alzheimer patients.
Academic Article Alzheimer-related neuronal protein A68: specificity and distribution.
Academic Article A.E. Bennett Research Award 1993. Olfactory neuroblasts from Alzheimer donors: studies on APP processing and cell regulation.
Academic Article Pathological stress granules in Alzheimer''s disease.
Academic Article RNA binding proteins and the genesis of neurodegenerative diseases.
Academic Article Depletion of microglia and inhibition of exosome synthesis halt tau propagation.
Academic Article Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis.
Academic Article Amylin receptor ligands reduce the pathological cascade of Alzheimer''s disease.
Grant Identification of Medicines That Moderate the Incidence of Alzheimer’s Disease
Academic Article Baseline Telomere Length and Effects of a Multidomain Lifestyle Intervention on Cognition: The FINGER Randomized Controlled Trial.
Academic Article Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology.
Academic Article Dysregulation of RNA Splicing in Tauopathies.
Academic Article Beneficial association of angiotensin-converting enzyme inhibitors and statins on the occurrence of possible Alzheimer''s disease after traumatic brain injury.
Academic Article Alzheimer''s disease: many failed trials, so where do we go from here?
Grant Systems-level functional proteomics analysis assemblies in Alzheimer's disease and mouse models of tauopathy
Grant Targeting Stress Granule Biology in Alzheimer's Disease
Grant RNA Binding Proteins in Alzheimer's Disease
Grant RNA binding proteins as novel targets in Alzheimer's disease
Grant Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins
Grant Regulation of RNA translation by MAPT in Alzheimer's disease

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  • Alzheimer Disease