Role of Heat Shock Proteins (HSP) in Neuroprotection for Ischemic Stroke

Abstract

Heat shock proteins (HSP) are upregulated early in response to many insults, including ischemic stroke. This upregulation allows cells to survive potentially lethal conditions via its chaperone functions which can assist in nascent protein folding and the prevention of protein aggregation. After ischemic stroke, HSP can directly interact with various proteins of the tightly regulated programmed cell death known as apoptosis. HSP70 also acts to modulate the inflammatory response following ischemic stroke. The 70 kDa inducible HSP also known as HSP70, has likely been the most extensively evaluated. HSP70 was shown to correlate to the phenomenon of induced tolerance. Studies in genetic mutant models or overexpression using gene transfer or heat stress, further showed that HSP70 led to improvements in brain cell survival. Pharmacological inducers of HSP70 demonstrated similar salutary effects in stroke models, and suggest that this approach has some translational value. Some of these pharmacological inducers have already been studied in humans for treatment of other conditions. Therefore, HSP seem to be neuroprotective, and should be further explored as a potential therapy against stroke and other neurodegenerative diseases.