title: Small heat shock proteins: Role in cellular functions and pathology.
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.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Raman
authors.initials: R
authors.lastname: Bakthisaran
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Tangirala
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: mohan@ccmb.res.in.
authors.forename: Ch Mohan
authors.initials: ChM
authors.lastname: Rao
mesh_terms: D000818:Animals; D002468:Cell Physiological Phenomena / Q000235:genetics*; D004194:Disease / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D050888:Heat-Shock Proteins, Small / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism; D013696:Temperature
chemical_list: D050888:Heat-Shock Proteins, Small; D018832:Molecular Chaperones
keywords: Anti-inflammatory property; Apoptosis; Cu(2+)-binding; Dynamic partitioning hypothesis; Molecular chaperone activity; Small heat shock proteins