Heat shock protein (HSP)

Heat shock proteins (HSPs) are a diverse family of highly conserved chaperone proteins that play central roles in cellular stress response, protein folding, prevention of aggregation, and recovery from damage due to environmental or physiological stress. They are named according to their molecular weight (such as Hsp60, Hsp70, Hsp90) and are induced by a variety of stresses, including heat, cold, toxins, hypoxia, and inflammation. HSPs maintain proteostasis by ensuring the correct folding of nascent proteins, refolding misfolded proteins, assisting in their transport across cellular compartments, and targeting damaged proteins for degradation. In addition to their classical chaperone functions, HSPs modulate apoptosis, immune response, and cell signaling, and they act as damage-associated molecular patterns (DAMPs) when found extracellularly, thereby influencing inflammation and immunity. HSPs are attractive therapeutic targets, particularly in oncology, where HSP90 inhibitors are in clinical development, as well as in neurodegenerative and inflammatory diseases where modulation of the chaperone system holds promise. “Heat shock protein” itself is a functional class; for therapeutic specificity, a particular HSP subtype (e.g., Hsp90 or Hsp70) should be used for downstream applications.

Other names

stress proteinHSPHSP70HSP90small heat shock protein (sHSP)chaperone proteinHsp27Hsp60Hsp100

Hsp90 inhibitors bind to the N-terminal ATP-binding domain, preventing chaperone activity and leading to the degradation of client oncoproteins. HSP70 inhibitors block ATPase activity, impairing protein folding and stress protection. Small molecules modulate HSP expression or function, either suppressing chaperone protection in cancer or boosting it in neurodegenerative diseases. Immunomodulation via extracellular HSP activation of immune cells.