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Updated: Jun 22, 2026

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
Aggregation-defective alpha-synuclein mutants inhibit the fibrillation of Parkinson's disease-linked alpha-synuclein
Hyun-Jung Koo1, Min Yeong Choi, Hana Im
1Department of Molecular Biology, Sejong University, 98 Gunja-dong, Kwangjin-gu, Seoul 143-747, Republic of Korea.
Abstract:
Alpha-synuclein comprises the fibrillar core of Lewy bodies, which is one of the histologically defining lesions of Parkinson's disease. Previously, we screened for alpha-synuclein substitution mutants that do not form fibrils. For preventative or therapeutic uses, it is essential to suppress the oligomerization/fibrillation of the wild-type and PD-linked alpha-synuclein proteins. Here we have examined the effects of fibrillation-retarded alpha-synuclein mutants on fibril formation by wild-type and PD-linked alpha-synuclein molecules. Six self-aggregation-defective alpha-synuclein mutants completely inhibit the fibrillation of both wild-type and Parkinson's disease-linked alpha-synuclein variants. These results suggest future applications for gene therapy: the transplantation of a fibrillation-blocking mutant alpha-synuclein gene into individuals who carry an early-onset PD-associated alpha-synuclein allele. Short synthetic peptides derived from these mutant sequences may also serve as a lead compound for the development of therapeutics for Parkinson's disease.
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