Introduction: The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury. Areas covered: In this review, we will focus on the role of Hsp70 in cell death and inflammation, and the current literature surrounding the pharmacological induction in acute ischemic stroke models with comments on potential applications at the clinical level. Expert opinion: Such neuroprotectants could be used to synergistically improve neurological outcome or to extend the time window of existing interventions, thus increasing the numbers of stroke victims eligible for treatment.
Bibliographical noteFunding Information:
This research was supported by grants from the National Institutes of Health (RO1 NS40516), and the Veteran’s Merit Award (I01 BX000589) to MA Yenari, Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03933017) to JY Kim, the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2017R1A2B2005350) to JE Lee and Seoul Clinical Laboratory Funding funded by Yonsei University College of Medicine (DUCR-000050) to YS Han. Grants to MA Yenari were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California.
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
- Clinical Biochemistry