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 hippocampal neurons (in culture)
Self-Described Keywords cell culture

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

Item TypeName
Concept Culture Media
Concept Motor Neurons
Concept Neurons
Concept Culture Techniques
Concept Dopaminergic Neurons
Concept Primary Cell Culture
Academic Article Transforming growth factor beta induces a beta-responsive calcium fluxes in neurons.
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 Changes in gene transcription during a beta-mediated cell death.
Academic Article FGF2 suppresses neuronogenesis of a cell line derived from rat olfactory epithelium.
Academic Article Physiologic levels of beta-amyloid activate phosphatidylinositol 3-kinase with the involvement of tyrosine phosphorylation.
Academic Article FMR1 gene expression in olfactory neuroblasts from two males with fragile X syndrome.
Academic Article The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity.
Academic Article Mechanisms of neurodegenerative disorders: Part 2: control of cell death.
Academic Article Continuous culture of neuronal cells from adult human olfactory epithelium.
Academic Article Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons.
Academic Article Hypoxia enhances beta-amyloid-induced apoptosis in rat cultured hippocampal neurons.
Academic Article Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.
Academic Article Beta/A4 domain of APP: antigenic differences between cell lines.
Academic Article Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients.
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 Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.
Academic Article Pathological proteins in Parkinson's disease: focus on the proteasome.
Academic Article Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein.
Academic Article LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans.
Academic Article Local RNA translation at the synapse and in disease.
Academic Article Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies.
Academic Article Alz-50 antibody recognizes Alzheimer-related neuronal changes.
Academic Article Neuronal-specific overexpression of a mutant valosin-containing protein associated with IBMPFD promotes aberrant ubiquitin and TDP-43 accumulation and cognitive dysfunction in transgenic mice.
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 The binding of kappa- and sigma-opiates in rat brain.
Academic Article Physiological levels of beta-amyloid increase tyrosine phosphorylation and cytosolic calcium.
Academic Article A.E. Bennett Research Award 1993. Olfactory neuroblasts from Alzheimer donors: studies on APP processing and cell regulation.
Academic Article ALS-linked mutations enlarge TDP-43-enriched neuronal RNA granules in the dendritic arbor.
Academic Article Mutations in LRRK2 potentiate age-related impairment of autophagic flux.
Academic Article A Parkinson''s disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity.
Academic Article LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts.
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 Impairment of PARK14-dependent Ca(2+) signalling is a novel determinant of Parkinson''s disease.
Academic Article Increased cytoplasmic TDP-43 reduces global protein synthesis by interacting with RACK1 on polyribosomes.
Academic Article Dioxins and related environmental contaminants increase TDP-43 levels.
Academic Article Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo.
Academic Article Changes in neuronal immunofluorescence in the C- versus N-terminal domains of hnRNP H following D1 dopamine receptor activation.
Academic Article Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology.
Academic Article TIA1 regulates the generation and response to toxic tau oligomers.
Academic Article The Evolution of Phase-Separated TDP-43 in Stress.
Academic Article Effects of Amylin Against Amyloid-ß-Induced Tauopathy and Synapse Loss in Primary Neurons.
Academic Article A Mutation in Hnrnph1 That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins.

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