Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders.

Serena Carra, Paola Rusmini, Valeria Crippa, Elisa Giorgetti, Alessandra Boncoraglio, Riccardo Cristofani, Maximillian Naujock, Melanie Meister, Melania Minoia, Harm H. Kampinga, Angelo Poletti

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The family of the mammalian small heat-shock proteins consists of 10 members (sHSPs/HSPBs: HSPB1-HSPB10) that all share a highly conserved C-terminal alpha-crystallin domain, important for the modulation of both their structural and functional properties. HSPB proteins are biochemically classified as molecular chaperones and participate in protein quality control, preventing the aggregation of unfolded or misfolded proteins and/or assisting in their degradation. Thus, several members of the HSPB family have been suggested to be protective in a number of neurodegenerative and neuromuscular diseases that are characterized by protein misfolding. However, the pro-refolding, anti-aggregation or pro-degradative properties of the various members of the HSPB family differ largely, thereby influencing their efficacy and protective functions. Such diversity depends on several factors, including biochemical and physical properties of the unfolded/misfolded client, the expression levels and the subcellular localization of both the chaperone and the client proteins. Furthermore, although some HSPB members are inefficient at inhibiting protein aggregation, they can still exert neuroprotective effects by other, as yet unidentified, manners; e.g. by maintaining the proper cellular redox state or/and by preventing the activation of the apoptotic cascade. Here, we will focus our attention on how the differences in the activities of the HSPB proteins can influence neurodegenerative and neuromuscular disorders characterized by accumulation of aggregate-prone proteins. Understanding their mechanism of action may allow us to target a specific member in a specific cell type/disease for therapeutic purposes.

Original languageEnglish
Pages (from-to)20110409
Number of pages1
JournalPhilosophical transactions of the Royal Society of London. Series B: Biological sciences
Volume368
Issue number1617
DOIs
Publication statusPublished - May 5 2013

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nervous system diseases
Nervous System Diseases
Agglomeration
protein
Proteins
neuromuscular disorders
proteins
neurodegenerative diseases
Neurodegenerative Diseases
Chaperonin 10
alpha-Crystallins
Small Heat-Shock Proteins
crystallins
neuroprotective effect
Neuromuscular Diseases
molecular chaperones
Molecular Chaperones
Neuroprotective Agents
protein aggregates
family

ASJC Scopus subject areas

  • Medicine(all)

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Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders. / Carra, Serena; Rusmini, Paola; Crippa, Valeria; Giorgetti, Elisa; Boncoraglio, Alessandra; Cristofani, Riccardo; Naujock, Maximillian; Meister, Melanie; Minoia, Melania; Kampinga, Harm H.; Poletti, Angelo.

In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences, Vol. 368, No. 1617, 05.05.2013, p. 20110409.

Research output: Contribution to journalArticle

Carra, S, Rusmini, P, Crippa, V, Giorgetti, E, Boncoraglio, A, Cristofani, R, Naujock, M, Meister, M, Minoia, M, Kampinga, HH & Poletti, A 2013, 'Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders.', Philosophical transactions of the Royal Society of London. Series B: Biological sciences, vol. 368, no. 1617, pp. 20110409. https://doi.org/10.1098/rstb.2011.0409
Carra, Serena ; Rusmini, Paola ; Crippa, Valeria ; Giorgetti, Elisa ; Boncoraglio, Alessandra ; Cristofani, Riccardo ; Naujock, Maximillian ; Meister, Melanie ; Minoia, Melania ; Kampinga, Harm H. ; Poletti, Angelo. / Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders. In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences. 2013 ; Vol. 368, No. 1617. pp. 20110409.
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