Heat shock 70 kDa protein 1A (HSPA1A) (HSPA1A)

Heat shock 70 kDa protein 1A (HSPA1A), commonly referred to as Hsp70 or Hsp72, is a central molecular chaperone and stress-inducible enzyme that plays a fundamental role in maintaining cellular proteostasis. It operates through an ATP-dependent cycle to assist in the folding of nascent proteins, the refolding of denatured polypeptides, and the directed degradation of misfolded proteins via the ubiquitin-proteasome system. In oncology, Hsp70 is frequently overexpressed, acting as a potent anti-apoptotic factor that stabilizes oncoproteins and promotes resistance to chemotherapy and radiation. In contrast, in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, Hsp70 activity is considered beneficial for the clearance of toxic protein aggregates, making its pharmacological induction a potential therapeutic strategy. Targeting Hsp70 involves small-molecule inhibitors that bind the N-terminal ATPase domain or allosteric sites to disrupt the chaperone cycle, though the high structural homology between inducible Hsp70 and the constitutive Hsc70 remains a significant challenge for achieving therapeutic selectivity and avoiding systemic toxicity.

Other names

Hsp70Hsp72Hsp70-1HspA1Heat shock protein 70HSP70.1Hsp70-1A

Inhibition of ATPase activity in the N-terminal nucleotide-binding domain (NBD), allosteric modulation of the C-terminal substrate-binding domain (SBD), or disruption of protein-protein interactions with co-chaperones such as Hsp40 and nucleotide exchange factors.