Mechanisms of Alpha-synuclein Aggregation and Toxicity
Annual rept. 1 Sep 2003-31 Aug 2004
BOSTON UNIV MA
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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 identified several novel interactions of Alpha-synuclein, including binding to the proteasome and selective inhibition of Mitochondrial complex 1. We have also identified a number of novel pathological changes associated with alpha-synuclein aggregation, including phosphorylation of tau protein and up-regulation of DJ-1 protein. Finally, our studies identify novel chemical and molecular strategies for inhibiting toxicity induced by aggregated alpha-synuclein.
- Anatomy and Physiology
- Medicine and Medical Research