Preventing α-synuclein aggregation: The role of the small heat-shock molecular chaperone proteins

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Review

Cox, Dezerae^1,2  Carver, John A.³  Ecroyd, Heath^1,2 

[1] Univ Wollongong, Sch Biol Sci, Wollongong, NSW 2522, Australia

[2] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia

[3] Australian Natl Univ, Res Sch Chem, Canberra, ACT 0200, Australia

关键词: alpha-Synuclein;    alpha B-crystallin;    Amyloid;    Protein aggregation;    Proteostasis;    Parkinson's disease;   

DOI  :  10.1016/j.bbadis.2014.06.024

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free