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Small Heat Shock Proteins and Human Neurodegenerative Diseases

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Abstract

The review discusses the role of small heat shock proteins (sHsps) in human neurodegenerative disorders, such as Charcot-Marie-Tooth disease (CMT), Parkinson’s and Alzheimer’s diseases, and different forms of tauopathies. The effects of CMT-associated mutations in two small heat shock proteins (HspB1 and HspB8) on the protein stability, oligomeric structure, and chaperone-like activity are described. Mutations in HspB1 shift the equilibrium between different protein oligomeric forms, leading to the alterations in its chaperone-like activity and interaction with protein partners, which can induce damage of the cytoskeleton and neuronal death. Mutations in HspB8 affect its interaction with the adapter protein Bag3, as well as the process of autophagy, also resulting in neuronal death. The impact of sHsps on different forms of amyloidosis is discussed. Experimental studies have shown that sHsps interact with monomers or small oligomers of amyloidogenic proteins, stabilize their structure, prevent their aggregation, and/or promote their specific proteolytic degradation. This effect might be due to the interaction between the β-strands of sHsps and β-strands of target proteins, which prevents aggregation of the latter. In cooperation with the other heat shock proteins, sHsps can promote disassembly of oligomers formed by amyloidogenic proteins. Despite significant achievements, further investigations are required for understanding the role of sHsps in protection against various neurodegenerative diseases.

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Abbreviations

ACD:

α-crystallin domain

CMT:

Charcot-Marie-Tooth disease

CTD:

C-terminal domain

NTD:

N-terminal domain

(s)Hsp:

(small) heat shock proteins

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Acknowledgements

All authors of this paper are alumni of the Department of Biochemistry, School of Biology, Moscow State University. Our investigation would have been impossible if not based on the knowledge and skills obtained in the course of our study at our department, on traditions laid by the founder of our department Academician Sergei E. Severin. In the year of the 80th anniversary of the Department of Biochemistry, we would like to wish our department great achievements and to voice the hope that in the future, despite all difficulties, the Department of Biochemistry will be able to educate interested and skillful biochemists.

Funding

This study was supported by the Russian Foundation for Basic Research (project 19-04-00038).

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Authors and Affiliations

  1. School of Biology, Department of Biochemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    L. K. Muranova, A. S. Ryzhavskaya, M. V. Sudnitsyna, V. M. Shatov & N. B. Gusev

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  1. L. K. Muranova
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  2. A. S. Ryzhavskaya
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  3. M. V. Sudnitsyna
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  4. V. M. Shatov
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  5. N. B. Gusev
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Correspondence to N. B. Gusev.

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The authors declare no conflict of interest in financial or any other area.

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This article does not contain studies with human participants or animals performed by any of the authors.

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 11, pp. 1564–1577.

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Muranova, L.K., Ryzhavskaya, A.S., Sudnitsyna, M.V. et al. Small Heat Shock Proteins and Human Neurodegenerative Diseases. Biochemistry Moscow 84, 1256–1267 (2019). https://doi.org/10.1134/S000629791911004X

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  • DOI: https://doi.org/10.1134/S000629791911004X

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