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Screening For Novel Inhibitors Of Αlpha-Ynuclein Seeded Nucleation-Dependent Aggregation And Toxicity As A Potential Therapeutic Strategy For Parkinson’S Disease, Mustafa Taleb Ardeh

Dissertations

α-Synuclein aggregation is the key pathogenic event in several important neurological disorders including Parkinson’s Disease, dementia with Lewy bodies and multiple system atrophy, giving rise to a distinct group of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been precisely elucidated, recent studies indicate that α-syn toxicity is mediated by a nucleation-dependent aggregation process. To elucidate the structural basis of α-synuclein mediated toxicity, we developed various methods to prepare different α-synuclein species of a defined size and morphology distribution, and we investigated their toxicity in different human dopaminergic cell lines. We observed that crude …