The Parkinson鈥檚 Disease-Associated H50Q Mutation Accelerates 伪-Synuclein Aggregation in Vitro

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• 作者：Dhiman Ghosh ; Mrityunjoy Mondal ; Ganesh M. Mohite ; Pradeep K. Singh ; Priyatosh Ranjan ; A. Anoop ; Saikat Ghosh ; Narendra Nath Jha ; Ashutosh Kumar ; Samir K. Maji
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：October 8, 2013
• 年：2013
• 卷：52
• 期：40
• 页码：6925-6927
• 全文大小：251K
• 年卷期：v.52,no.40(October 8, 2013)
• ISSN：1520-4995

文摘

伪-Synuclein (伪-Syn) aggregation is directly linked with Parkinson鈥檚 disease (PD) pathogenesis. Here, we analyzed the aggregation of newly discovered 伪-Syn missense mutant H50Q in vitro and found that this mutation significantly accelerates the aggregation and amyloid formation of 伪-Syn. This mutation, however, did not alter the overall secondary structure as suggested by two-dimensional nuclear magnetic resonance and circular dichroism spectroscopy. The initial oligomerization study by cross-linking and chromatographic techniques suggested that this mutant oligomerizes to an extent similar to that of the wild-type 伪-Syn protein. Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD.