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

Journal Article


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Abstract


  • 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 α-synuclein into Lewy bodies and Lewy neuritis is associated with neurodegenerative diseases classified as α-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 α-synuclein aggregation, yet these fail to do so in the context of the α-synucleinopathies. This review discusses how sHsps interact with α-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 α-synuclein escaping the sHsp chaperones in the context of the α-synucleinopathies.

Publication Date


  • 2014

Citation


  • Cox, D., Carver, J. A. & Ecroyd, H. (2014). Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins. BBA: Molecular Basis of Disease, 1842 (9), 1830-1843.

Scopus Eid


  • 2-s2.0-84904431211

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3455&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2436

Has Global Citation Frequency


Number Of Pages


  • 13

Start Page


  • 1830

End Page


  • 1843

Volume


  • 1842

Issue


  • 9

Place Of Publication


  • Netherlands

Abstract


  • 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 α-synuclein into Lewy bodies and Lewy neuritis is associated with neurodegenerative diseases classified as α-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 α-synuclein aggregation, yet these fail to do so in the context of the α-synucleinopathies. This review discusses how sHsps interact with α-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 α-synuclein escaping the sHsp chaperones in the context of the α-synucleinopathies.

Publication Date


  • 2014

Citation


  • Cox, D., Carver, J. A. & Ecroyd, H. (2014). Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins. BBA: Molecular Basis of Disease, 1842 (9), 1830-1843.

Scopus Eid


  • 2-s2.0-84904431211

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3455&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2436

Has Global Citation Frequency


Number Of Pages


  • 13

Start Page


  • 1830

End Page


  • 1843

Volume


  • 1842

Issue


  • 9

Place Of Publication


  • Netherlands