Hsp90 Protein (Heat Shock Protein 90) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox .infobox .infobox-protein
| protein_name = HSP90 (Heat Shock Protein 90)
| gene = HSP90AA1 / HSP90AB1
| uniprot = P07900 / P08238
| pdb_ids = 2IOJ, 1YER, 3T0H
| molecular_weight = ~90 kDa
| subcellular_cytoplasm = Cytoplasm, ER, mitochondria
| protein_family = Hsp90 family
}}
HSP90 (Heat Shock Protein 90) is a highly abundant molecular chaperone protein that constitutes 1-2% of total cellular protein. It plays a critical role in protein folding, stabilization, and quality control by assisting the refolding of misfolded proteins and preventing aggregation. HSP90 is particularly important in neurodegenerative diseases as it helps manage proteotoxic stress from misfolded Aβ, tau, α-synuclein, and mutant huntingtin proteins.
HSP90 is a dimeric protein with each monomer containing:
| Approach | Agent/Strategy | Status | Mechanism |
|---|---|---|---|
| HSP90 inhibitors | Geldanamycin | Preclinical | Binds N-terminal pocket, blocks ATPase |
| HSP90 inhibitors | 17-AAG (Tanespimycin) | Clinical trials (oncology) | N-terminal inhibitor |
| HSP90 inhibitors | 17-DMAG (Alvespimycin) | Preclinical | N-terminal inhibitor |
| HSP90 inhibitors | PU-H71 | Preclinical | Purine scaffold inhibitor |
| HSP90 activators | Natural compounds | Preclinical | Increase HSP90 expression |
| Co-chaperone modulators | p23 inhibitors | Preclinical | Disrupt client loading |
Pratt WB, Toft DO. (2003). "Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone system." Exp Biol Med. PMID:14527341 - Comprehensive review of HSP90 mechanism.
Luo W, et al. (2007). "Hsp90 alpha and Hsp90 beta have distinct functions in vivo." Cell. PMID:17409246 - Isoform-specific functions.
Dou F, et al. (2009). "Chaperone networks for protein misfolding in Alzheimer's disease." Antioxid Redox Signal. PMID:19365770 - HSP90 in AD pathophysiology.
Brehme M, et al. (2014). "A chaperome network overhaul in aging and neurodegeneration." Cell. PMID:25417108 - Chaperome changes in aging brains.
Thibaudeau TA, Smith DM. (2019). "A practical review of the emerging Hsp90 inhibitors, ATP non-competitive." Adv Cancer Res. PMID:30698709 - Therapeutic targeting strategies.
This page was created to expand protein coverage in NeuroWiki. Last updated: 2026-03-03
The study of Hsp90 Protein (Heat Shock Protein 90) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.