The role and therapeutic potential of Hsp90, Hsp70, and smaller heat shock proteins in peripheral and central neuropathies
Heat shock proteins (Hsps) are molecular chaperones that also play important roles in the activation of the heat shock response (HSR). The HSR is an evolutionary conserved and protective mechanism that is used to counter abnormal physiological conditions, stressors, and disease states, such as those...
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Published in | Medicinal research reviews Vol. 41; no. 1; pp. 202 - 222 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
Wiley Subscription Services, Inc
01.01.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Heat shock proteins (Hsps) are molecular chaperones that also play important roles in the activation of the heat shock response (HSR). The HSR is an evolutionary conserved and protective mechanism that is used to counter abnormal physiological conditions, stressors, and disease states, such as those exemplified in cancer and/or neurodegeneration. In normal cells, heat shock factor‐1 (HSF‐1), the transcription factor that regulates the HSR, remains in a dormant multiprotein complex that is formed upon association with chaperones (Hsp90, Hsp70, etc.), co‐chaperones, and client proteins. However, under cellular stress, HSF‐1 dissociates from Hsp90 and induces the transcriptional upregulation of Hsp70 to afford protection against the encountered cellular stress. As a consequence of both peripheral and central neuropathies, cellular stress occurs and results in the accumulation of unfolded and/or misfolded proteins, which can be counterbalanced by activation of the HSR. Since Hsp90 is the primary regulator of the HSR, modulation of Hsp90 by small molecules represents an attractive therapeutic approach against both peripheral and central neuropathies. |
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Bibliography: | Subhabrata Chaudhury and Bradley M. Keegan should be considered the joint first authors. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-2 SC and BMK should be considered joint first author |
ISSN: | 0198-6325 1098-1128 |
DOI: | 10.1002/med.21729 |