* To whom correspondence should be addressed.
Received March 30, 2019; Revised May 4, 2019; Accepted June 27, 2019
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.
KEY WORDS: small heat shock proteins, chaperone-like activity, amorphous aggregation, β-amyloids, posttranslational modifications, neurodegenerative diseases