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SMC

Seminar

Factors affecting the aggregation of the natively unfolded protein alpha-synuclein

Fink, AL (California)
Monday 21 June 2004, 14:30-15:30

Seminar Room 1, Newton Institute

Abstract

The etiology of Parkinson’s disease is unknown; however, substantial evidence implicates the aggregation of alpha-synuclein as playing a critical role in the disease. We have found that a variety of endogenous and exogenous factors induce a conformational change in alpha-synuclein and directly accelerate the rate of formation of alpha-synuclein fibrils in vitro; other factors inhibit the fibrillation. The mechanism of alpha-synuclein aggregation involves at last three competing kinetic pathways, leading to fibrils, amorphous aggregates, and soluble oligomers. Thus, many factors may cause acceleration of alpha-synuclein fibrillation, and some of these factors are likely to be important in the pathophysiology of alpha-synuclein and Parkinson’s disease. Various aspects of how the self-assembly of alpha-synuclein occurs will be discussed.

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