Mechanisms of alpha-Synuclein Aggregation and Toxicity

Abstract

Alpha-synuclein is a protein implicated in the pathophysiology of Parkinson's disease. The purpose of this proposal is to study the regulation of synuclein aggregation by metals, the interaction of synuclein with other proteins associated with its pathophysiology and the effects of aggregated alpha-synuclein on the function of neuronal mitochondria. During the current year, we have studied the regulation of synuclein aggregation and toxicity in vitro. We examined the response of synuclein to metals, as well as to other toxins. We observed that inhibitors of mitochondrial complex I are the most effective agents for inducing synuclein fibrillization and toxicity in vivo (in C. elegans). We also used C. elegans to explore novel mechanisms of therapy. We demonstrated that D-Beta-hydroxybutyrate, TUDCA and probucol were all protective against synuclein toxicity. Both TUDCA and probucol are FDA approved medications that could be readily translated towards clinical use.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2006
Accession Number
ADA467589

Entities

People

  • Benjamin Wolozin

Organizations

  • Boston University

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Birds
  • Brain
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Free Radicals
  • Neurodegeneration
  • Neurodegenerative Diseases
  • Neurons
  • Organic Chemistry
  • Parkinson'S Disease
  • Proteomics

Fields of Study

  • Biology

Readers

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  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.