Publication

The family of mammalian small heat shock proteins (HSPBs): Implications in protein deposit diseases and motor neuropathies

Boncoraglio, A., Minoia, M. & Carra, S., Oct-2012, In : International journal of biochemistry & cell biology. 44, 10, p. 1657-1669 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Alessandra Boncoraglio
  • Melania Minoia
  • Serena Carra

A number of neurological and muscular disorders are characterized by the accumulation of aggregate-prone proteins and are referred to as protein deposit or protein conformation diseases. Besides some sporadic forms, most of them are genetically inherited in an autosomal dominant manner, although recessive forms also exist. Although genetically very heterogeneous, some of these diseases are the result of mutations in some members of the mammalian small heat shock protein family (sHSP/HSPB), which are key players of the protein quality control system and participate, together with other molecular chaperones and co-chaperones, in the maintenance of protein homeostasis. Thus, on one hand upregulation of specific members of the HSPB family can exert protective effects in protein deposit diseases, such as the polyglutamine diseases. On the other hand, mutations in the HSPBs lead to neurological and muscular disorders, which may be due to a loss-of-function in protein quality control and/or to a gain-of-toxic function, resulting from the aggregation-proneness of the mutants. In this review we summarize the current knowledge about some of the best characterized functions of the HSPBs (e.g. role in cytoskeleton stabilization, chaperone function, anti-aggregation and anti-apoptotic activities), also highlighting differences in the properties of the various HSPBs and how these may counteract protein aggregation diseases. We also describe the mutations in the various HSPBs associated with neurological and muscular disorders and we discuss how gain-of-toxic function mechanisms (e.g. due to the mutated HSPB protein instability and aggregation) and/or loss-of-function mechanisms can contribute to HSPB-associated pathologies. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology. (C) 2012 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1657-1669
Number of pages13
JournalInternational journal of biochemistry & cell biology
Volume44
Issue number10
Publication statusPublished - Oct-2012

    Keywords

  • Small heat shock proteins, Protein aggregation, Protein degradation, Neuropathy, Myopathy, Congenital cataract, ALPHA-B-CRYSTALLIN, MARIE-TOOTH-DISEASE, SPINAL MUSCULAR-ATROPHY, DESMIN-RELATED MYOPATHY, HUMAN NEUROMUSCULAR DISORDERS, CHAPERONE-LIKE FUNCTION, C-DEPENDENT ACTIVATION, LENS EPITHELIAL-CELLS, PARALYZE MOUSE MUTANT, MOLECULAR CHAPERONES

ID: 5648030