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Updated: Oct 6, 2025
Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
Published on: January 20, 2023
Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing
Siarhei A Dabravolski1, Vasily N Sukhorukov2,3, Vladislav A Kalmykov2,4
1Department of Clinical Diagnostics, Vitebsk State Academy of Veterinary Medicine [UO VGAVM], 7/11 Dovatora Str., 210026 Vitebsk, Belarus.
Insights
Heat shock protein 90 (HSP90) plays a key role in protecting the heart from damage and aging. This review explores HSP90
Area of Science:
- Cardiovascular science
- Molecular biology
- Aging research
Background:
- Cardiovascular diseases (CVDs) are the leading global cause of death.
- Molecular chaperones, including Heat Shock Protein 90 (HSP90), are crucial for cellular protection against stress and protein misfolding in the heart.
- HSP90 isoforms (HSP90a, HSP90b, TRAP1, Grp94) support the heart's high metabolic demands.
Purpose of the Study:
- To review the recent findings on the role of HSP90 proteins in cardioprotection.
- To discuss the involvement of HSP90 in atherosclerosis and cardiovascular disease (CVD) development.
- To explore how HSP90 clients activate molecular pathways related to heart aging.
Main Methods:
- Literature review of recent scientific investigations.
- Analysis of studies on HSP90 inhibitors and their mechanisms.
- Examination of HSP90 client protein involvement in cellular signaling.
Main Results:
- HSP90 proteins are integral to cardioprotection and mitigating age-related cardiac decline.
- HSP90 influences atherosclerosis and the progression of cardiovascular diseases.
- HSP90 client proteins mediate key signaling pathways implicated in heart aging.
Conclusions:
- HSP90 is a significant factor in maintaining heart health and combating cardiovascular diseases.
- Targeting HSP90 pathways offers potential therapeutic strategies for heart aging and CVDs.
- Further research into HSP90's molecular mechanisms is essential for developing novel cardioprotective interventions.
Abstract:
Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.
