期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 425, 期 22, 页码 4614-4628出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2013.08.006
关键词
thioflavin T assay; amyloid; cytoprotective; aggregation; Parkinson's disease
资金
- BP Centenary- Murray Edwards College Scholarship
- Cambridge Commonwealth Trust
- Department of Chemistry
- Wellcome Trust
- Dorothy Hodgkin Royal Society Fellowship
- Medical Research Council [MC_U117533887] Funding Source: researchfish
- MRC [MC_U117533887] Funding Source: UKRI
Aggregated alpha a-synuclein is one of the main components of the pathological Lewy bodies associated with Parkinson's disease (PD). Many other proteins, including chaperones such as Hsp90 and Hsp70, have been found co-localized with Lewy bodies and the expression levels of Hsp90 have been found to be increased in brains of PD patients. Although the role of Hsp70 in the aggregation of alpha-synuclein has been extensively studied, relatively little is known about the effect of Hsp90 on this process. Here, we have investigated if Hsp90 can prevent the aggregation of the A53T pathological mutant of alpha-synuclein in vitro. A detailed study using many biophysical methods has revealed that Hsp90 prevents alpha-synuclein from aggregating in an ATP-independent manner and that it forms a strong complex with the transiently populated toxic oligomeric alpha-synuclein species formed along the aggregation pathway. We have also shown that, upon forming a complex with Hsp90, the oligomers are rendered harmless and nontoxic to cells. Thus, we have clear evidence that Hsp90 is likely to play an important role on these processes in vivo. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据