Heat shock protein 70 (HSP70) (HSP70)

Heat shock protein 70 (HSP70) is a highly conserved family of molecular chaperones essential for maintaining cellular proteostasis by assisting in protein folding, refolding, and degradation [1.2.2, 1.3.2]. As a key component of the heat shock response (HSR) pathway, HSP70 expression is primarily regulated by the transcription factor HSF1 and is rapidly induced by stressors such as heat, oxidative stress, and proteotoxic insults [1.1.5, 1.5.3]. In oncology, HSP70 is frequently overexpressed and acts as a potent anti-apoptotic factor, stabilizing oncogenic proteins and allowing tumor cells to survive under harsh conditions and resist chemotherapy [1.2.1, 1.2.3]. Conversely, in neurodegenerative diseases like Alzheimer's and Parkinson's, the decline of HSP70 activity contributes to the accumulation of toxic protein aggregates, making its induction a potential therapeutic strategy [1.1.2, 1.2.5]. Pharmacological modulation of HSP70 includes small-molecule inhibitors that block its ATPase activity or disrupt its interactions with co-chaperones, as well as activators like arimoclomol that enhance its protective functions [1.5.1, 1.5.4]. Despite its therapeutic potential, developing selective HSP70 modulators remains challenging due to the high conservation among its 13 human isoforms and its essential roles in normal cellular physiology [1.3.3, 1.4.1].

Other names

HSPA70 kDa heat shock proteinChaperone protein HSP70HSPA1AHSPA1BHSPA1LHeat shock cognate 70 (Hsc70)HSPA8Binding immunoglobulin protein (BiP)Grp78HSPA5MortalinGrp75HSPA9

Drugs targeting HSP70 primarily act by inhibiting its ATPase activity (ATP-competitive), allosterically modulating substrate binding, or disrupting protein-protein interactions with co-chaperones such as J-proteins and nucleotide exchange factors [1.5.1, 1.5.4]. In neurodegenerative contexts, therapeutic strategies may also involve the induction of the heat shock response via HSF1 activation to increase HSP70 levels and enhance proteostatic capacity [1.1.5, 1.5.2].