AHSA1 Protein is a protein encoded by the [AHSA1](/genes/ahsa1) gene that ahsa1 functions as a molecular co-chaperone:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
AHSA1 (Activator of Hsp90 ATPase Homolog 1) is a co-chaperone that stimulates the ATPase activity of Hsp90, facilitating the folding and maturation of client proteins.
AHSA1 Protein is a protein encoded by the [AHSA1](/genes/ahsa1) gene that ahsa1 functions as a molecular co-chaperone:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
AHSA1 (Activator of Hsp90 ATPase Homolog 1) is a co-chaperone that stimulates the ATPase activity of Hsp90, facilitating the folding and maturation of client proteins.
Protein Infobox
Structure
AHSA1 is a 338-amino acid protein consisting of two main domains:
N-terminal domain: Binds to Hsp90 and stimulates its ATPase activity
C-terminal domain: Contains the catalytic center for ATP hydrolysis stimulation
The protein forms a dimer that can bind to Hsp90 dimer
Normal Function
AHSA1 functions as a molecular co-chaperone:
ATPase stimulation: Accelerates Hsp90 ATP hydrolysis 10-fold
Client protein maturation: Facilitates folding of Hsp90 client proteins
Protein quality control: Helps prevent aggregation of misfolded proteins
Cellular proteostasis: Essential for maintaining protein homeostasis
Role in Neurodegeneration
Alzheimer's Disease
Hsp90-mediated [tau](/proteins/tau) aggregation is implicated in AD pathology
AHSA1 levels are altered in AD brains
Modulating Hsp90-AHSA1 interaction may affect tau pathology
Hsp90 inhibitors are being explored for AD therapy
Modulating co-chaperone activity may influence aggregation
Therapeutic targeting of Hsp90 complex is being explored
Therapeutic Targeting
Hsp90 inhibitors: Ganetespib, Onalespib (in cancer trials)
AHSA1 modulators: Being developed to specifically modulate co-chaperone function
Combination therapy: Hsp90 inhibitors with proteasome inhibitors
Key Publications
[@panaretou2002]: Panaretou B, et al. [Activation of the ATPase activity of hsp90 by the co-chaperone Cdc37 and p23](https://pubmed.ncbi.nlm.nih.gov/11907279/). Mol Cell. 2002;10(6):1307-1318.
[@retzlaff2009]: Retzlaff M, et al. [Hsp90 is regulated by a switch in its functional cycle](https://pubmed.ncbi.nlm.nih.gov/19344235/). Nat Cell Biol. 2009;11(9):1083-1090.
[@luo2020]: Luo W, et al. [Hsp90 and cochaperones in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/31630911/). Adv Exp Med Biol. 2020;1243:87-107.
[@chen2016]: Chen B, et al. [Targeting Hsp90 for Alzheimer's disease therapy](https://pubmed.ncbi.nlm.nih.gov/26647310/). Future Med Chem. 2016;8(1):11-15.