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.
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.
Pathway Diagram
Mermaid diagram (expand to render)
Knowledge graph relationships for HSP90 (315 total edges in KG)
Brain Atlas Resources
The [Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=HSP90AA1) provides gene expression data for HSP90AA1:
Human Brain Expression: Searchable expression data across brain regions
Cell Type Specificity: Expression patterns in different neuronal populations
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](/proteins/amyloid-beta), [tau](/proteins/tau), α-synuclein, and mutant [huntingtin](/genes/htt) proteins.
Structure
HSP90 is a dimeric protein with each monomer containing:
N-terminal ATPase domain (1-220 aa): Binds and hydrolyzes ATP; target of many small-molecule inhibitors
Middle domain (220-370 aa): Client protein binding site; contains catalytic loop for ATP hydrolysis
HSP90 directly interacts with mutant [huntingtin](/proteins/huntingtin) (mHtt)
Facilitates folding of polyglutamine-expanded proteins
HSP90 inhibition promotes clearance of mHtt aggregates
Co-chaperone DNAJB6 more effective at preventing aggregation
Amyotrophic Lateral Sclerosis
Manages mutant SOD1 aggregation in familial ALS
[TDP-43](/mechanisms/tdp-43-proteinopathy) and FUS are HSP90 client proteins
HSP90 inhibitors reduce TDP-43 aggregation
Therapeutic Targeting
Key Publications
Pratt WB, Toft DO. (2003). "Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone system." Exp Biol Med. PMID: 14527341(https://pubmed.ncbi.nlm.nih.gov/14527341/) - Comprehensive review of HSP90 mechanism.
Luo W, et al. (2007). "Hsp90 alpha and Hsp90 beta have distinct functions in vivo." Cell. PMID: 17409246(https://pubmed.ncbi.nlm.nih.gov/17409246/) - Isoform-specific functions.
Dou F, et al. (2009). "Chaperone networks for protein misfolding in Alzheimer's disease." Antioxid Redox Signal. PMID: 19365770(https://pubmed.ncbi.nlm.nih.gov/19365770/) - HSP90 in AD pathophysiology.
Brehme M, et al. (2014). "A chaperome network overhaul in aging and neurodegeneration." Cell. PMID: 25417108(https://pubmed.ncbi.nlm.nih.gov/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(https://pubmed.ncbi.nlm.nih.gov/30698709/) - Therapeutic targeting strategies.
Cross-links
[Protein Quality Control Network](/mechanisms/protein-quality-control-network) - HSP90 is central component
This page was created to expand protein coverage in NeuroWiki. Last updated: 2026-03-03
Background
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.
[Zuo J, et al, HSP90 and neurodegenerative diseases (2015)](https://pubmed.ncbi.nlm.nih.gov/25850067/)
[Lackie RE, et al, The HSP90 molecular chaperone network in neurodegeneration (2020)](https://pubmed.ncbi.nlm.nih.gov/31710195/)
[Luo W, et al, HSP90 inhibitors in neurodegenerative diseases (2020)](https://pubmed.ncbi.nlm.nih.gov/32762761/)
[Taylor SE, et al, HSP90 and tauopathy (2021)](https://pubmed.ncbi.nlm.nih.gov/33497962/)
Pathway Diagram
The following diagram shows the key molecular relationships involving HSP90 Protein (Heat Shock Protein 90) discovered through SciDEX knowledge graph analysis: