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) : Wolozin, Benjamin


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a467589.pdf


Report Date : Sep 2006


Pagination or Media Count : 90


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.


Descriptors :   *PARKINSONS DISEASE , METALS , BRAIN , TOXICITY , PROTEINS , NERVE CELLS , PATHOPHYSIOLOGY , MITOCHONDRIA


Subject Categories : Toxicology


Distribution Statement : APPROVED FOR PUBLIC RELEASE