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The two-faced nature of small heat-shock proteins: Amyloid fibril assembly and the inhibition of fibril formation. Relevance to disease states

Chapter


Abstract


  • The ability of small heat-shock proteins (sHsps) such as αB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered β-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzheimer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. It has been shown, however, that sHsps are potent inhibitors of fibril formation of a range of target proteins. In this chapter, the disease-related significance of this observation is discussed. Interestingly, in addition to being effective molecular chaperones, αA- and αB-crystallin themselves, along with some of their peptide fragments, readily form amyloid fibrils under slightly destabilising solution conditions. The implications of this observation in terms of protein conformational diseases, e.g. cataract, along with the potential nanotechnological applications of these fibrils, are discussed. © 2012 Nova Science Publishers, Inc. All rights reserved.

Publication Date


  • 2011

Citation


  • Ecroyd, H., Meehan, S., & Carver, J. A. (2011). The two-faced nature of small heat-shock proteins: Amyloid fibril assembly and the inhibition of fibril formation. Relevance to disease states. In Small Stress Proteins and Human Diseases (pp. 189-211).

International Standard Book Number (isbn) 13


  • 9781614706366

Scopus Eid


  • 2-s2.0-84895392709

Web Of Science Accession Number


Book Title


  • Small Stress Proteins and Human Diseases

Start Page


  • 189

End Page


  • 211

Abstract


  • The ability of small heat-shock proteins (sHsps) such as αB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered β-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzheimer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. It has been shown, however, that sHsps are potent inhibitors of fibril formation of a range of target proteins. In this chapter, the disease-related significance of this observation is discussed. Interestingly, in addition to being effective molecular chaperones, αA- and αB-crystallin themselves, along with some of their peptide fragments, readily form amyloid fibrils under slightly destabilising solution conditions. The implications of this observation in terms of protein conformational diseases, e.g. cataract, along with the potential nanotechnological applications of these fibrils, are discussed. © 2012 Nova Science Publishers, Inc. All rights reserved.

Publication Date


  • 2011

Citation


  • Ecroyd, H., Meehan, S., & Carver, J. A. (2011). The two-faced nature of small heat-shock proteins: Amyloid fibril assembly and the inhibition of fibril formation. Relevance to disease states. In Small Stress Proteins and Human Diseases (pp. 189-211).

International Standard Book Number (isbn) 13


  • 9781614706366

Scopus Eid


  • 2-s2.0-84895392709

Web Of Science Accession Number


Book Title


  • Small Stress Proteins and Human Diseases

Start Page


  • 189

End Page


  • 211