期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1842, 期 9, 页码 1830-1843出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2014.06.024
关键词
alpha-Synuclein; alpha B-crystallin; Amyloid; Protein aggregation; Proteostasis; Parkinson's disease
资金
- Australian Postgraduate Award
- Australian Research Council Future Fellowship [FT110100586]
- Australian Department of Health and Ageing grant
- Australian National Health and Medical Research Council project grant [1068087]
Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. The failure of proteostasis can result in the accumulation of non-native proteins leading to their aggregation and deposition in cells and in tissues. The amyloid fibrillar aggregation of the protein a-synuclein into Lewy bodies and Lewy neuritis is associated with neurodegenerative diseases classified as alpha-synucleinopathies, which include Parkinson's disease and dementia with Lewy bodies. The small heat-shock proteins (sHsps) are molecular chaperones that are one of the cell's first lines of defence against protein aggregation. They act to stabilise partially folded protein intermediates, in an ATP-independent manner, to maintain cellular proteostasis under stress conditions. Thus, the sHsps appear ideally suited to protect against alpha-synuclein aggregation, yet these fail to do so in the context of the alpha-synucleinopathies. This review discusses how sHsps interact with alpha-synuclein to prevent its aggregation and, in doing so, highlights the multi-faceted nature of the mechanisms used by sHsps to prevent the fibrillar aggregation of proteins. It also examines what factors may contribute to a-synuclein escaping the sHsp chaperones in the context of the alpha-synucleinopathies. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.
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