Accession Number:

ADA467589

Title:

Mechanisms of alpha-Synuclein Aggregation and Toxicity

Descriptive Note:

Final rept. 1 Sep 2001-31 Aug 2006

Corporate Author:

BOSTON UNIV MA

Personal Author(s):

Report Date:

2006-09-01

Pagination or Media Count:

90.0

Abstract:

Alpha-synuclein is a protein implicated in the pathophysiology of Parkinsons 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.

Subject Categories:

  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE