Heat shock proteins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic implications

Cerebral ischemia-reperfusion injury (CIRI) remains a significant challenge in ischemic stroke treatment. Heat shock proteins (HSPs), a cadre of molecular chaperones, have emerged as pivotal regulators in this pathological cascade. This review synthesizes the latest research on HSPs in CIRI from 2013 to 2024 focusing on their multifaceted roles and therapeutic potential. We explore the diverse cellular functions of HSPs, including regulation of oxidative stress, apoptosis, necroptosis, ferroptosis, autophagy, neuroinflammation, and bloodbrain barrier integrity. Key HSPs, such as HSP90, HSP70, HSP32, HSP60, HSP47, and small HSPs, are investigated for their specific mechanisms of action in CIRI. Potential therapeutic strategies targeting HSPs, including HSP inhibitors, traditional Chinese medicine components, and gene therapy, are discussed. This review provides a comprehensive understanding of HSPs in CIRI and offers insights into the development of innovative neuroprotective treatments.