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Biochim Biophys Acta. 2015 Apr;1854(4):291-319. doi: 10.1016/j.bbapap.2014.12.019. Epub 2014 Dec 30.

Small heat shock proteins: Role in cellular functions and pathology.

Author information

1
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
2
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: mohan@ccmb.res.in.

Abstract

Small heat shock proteins (sHsps) are conserved across species and are important in stress tolerance. Many sHsps exhibit chaperone-like activity in preventing aggregation of target proteins, keeping them in a folding-competent state and refolding them by themselves or in concert with other ATP-dependent chaperones. Mutations in human sHsps result in myopathies, neuropathies and cataract. Their expression is modulated in diseases such as Alzheimer's, Parkinson's and cancer. Their ability to bind Cu2+, and suppress generation of reactive oxygen species (ROS) may have implications in Cu2+-homeostasis and neurodegenerative diseases. Circulating αB-crystallin and Hsp27 in the plasma may exhibit immunomodulatory and anti-inflammatory functions. αB-crystallin and Hsp20 exhitbit anti-platelet aggregation: these beneficial effects indicate their use as potential therapeutic agents. sHsps have roles in differentiation, proteasomal degradation, autophagy and development. sHsps exhibit a robust anti-apoptotic property, involving several stages of mitochondrial-mediated, extrinsic apoptotic as well as pro-survival pathways. Dynamic N- and C-termini and oligomeric assemblies of αB-crystallin and Hsp27 are important factors for their functions. We propose a "dynamic partitioning hypothesis" for the promiscuous interactions and pleotropic functions exhibited by sHsps. Stress tolerance and anti-apoptotic properties of sHsps have both beneficial and deleterious consequences in human health and diseases. Conditional and targeted modulation of their expression and/or activity could be used as strategies in treating several human disorders. The review attempts to provide a critical overview of sHsps and their divergent roles in cellular processes particularly in the context of human health and disease.

KEYWORDS:

Anti-inflammatory property; Apoptosis; Cu(2+)-binding; Dynamic partitioning hypothesis; Molecular chaperone activity; Small heat shock proteins

PMID:
25556000
DOI:
10.1016/j.bbapap.2014.12.019
[Indexed for MEDLINE]
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