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

Heath Ecroyd, Sarah Meehan, John A. Carver*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Title of host publicationSmall Stress Proteins and Human Diseases
PublisherNova Science Publishers, Inc.
Pages189-211
Number of pages23
ISBN (Print)9781614706366
Publication statusPublished - 2011
Externally publishedYes

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