Evaluating synthetic fragments of α-synuclein for influence on α-synuclein aggregation behavior

WCC 21

Cynthia Crosswhite1, Kate Walsham1, Margaret Blattner2, and Julia H Miwa, jmiwa@wellesley.edu2. (1) Wellesley College, 21 Wellesley College Rd., Wellesley, MA 02481, (2) Department of Chemistry, Wellesley College, Wellesley, MA 02481
Parkinson's disease is a neurodegenerative disorder that is characterized by the depletion of dopamine linked to the presence of Lewy bodies in the substantia nigra. These fibrillar cytoplasmic inclusions are primarily composed of α-synuclein. The function of α-synuclein is currently unknown, but α-synuclein aggregation has been linked to the etiology of Parkinson's disease. The project goals are to identify key fragments of α-synuclein that affect aggregation and to identify key lysine residues that influence aggregation behavior. There are three phases in the project strategy: synthesizing fragments of α-synuclein and testing for inhibition of aggregation of the whole protein, replacing lysine residues with alanine residues in active fragments, and incorporating lysine residues modified with a small molecule into active peptide fragments. As the aggregation behavior in the presence and absence of the fragments is compared, we hope to increase the understanding of α-synuclein aggregation behavior in the progression of Parkinson's disease.