Epichaperomes: Redefining chaperone biology and therapeutic strategies in complex diseases Review
| Authors: | Pasala, C.; Digwal, C. S.; Sharma, S.; Wang, S.; Bubula, A.; Chiosis, G. |
| Review Title: | Epichaperomes: Redefining chaperone biology and therapeutic strategies in complex diseases |
| Abstract: | The complexity of disease biology extends beyond mutations or overexpression, encompassing stress-induced mechanisms that reshape proteins into pathological assemblies. Epichaperomes, stable and disease-specific assemblies of chaperones and co-chaperones, exemplify this phenomenon. This review emphasizes the critical structural and functional distinctions between epichaperomes and canonical chaperones, highlighting their role in redefining therapeutic strategies. Epichaperomes arise under stress conditions through post-translational modifications that stabilize these assemblies, enabling them to act as scaffolding platforms that rewire protein-protein interaction networks and drive the pathological phenotypes of complex diseases such as cancer and neurodegeneration. Chemical biology has been instrumental in uncovering the unique nature of epichaperomes, with small molecules like PU-H71 elucidating their biology and demonstrating their therapeutic potential by dismantling pathological scaffolds and restoring normal protein-protein interaction networks. By targeting epichaperomes, we unlock the potential for network-level interventions and personalized medicine, offering transformative possibilities for diseases driven by protein-protein interaction network dysregulation. © 2025 RSC. |
| Keywords: | human cell; review; nonhuman; phenotype; protein protein interaction; drug development; protein processing; drug therapy; therapy; personalized medicine; nerve degeneration; chaperone; prevention; etiology; human; zelavespib |
| Journal Title: | RSC Chemical Biology |
| Volume: | 6 |
| Issue: | 5 |
| ISSN: | 2633-0679 |
| Publisher: | Royal Society of Chemistry |
| Date Published: | 2025-05-01 |
| Start Page: | 678 |
| End Page: | 698 |
| Language: | English |
| DOI: | 10.1039/d5cb00010f |
| PROVIDER: | scopus |
| PMCID: | PMC11933791 |
| PUBMED: | 40144950 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Gabriela Chiosis -- Source: Scopus |
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