Heat shock proteins and neuroprotection

In response to many metabolic disturbances and injuries including stroke, neurodegenerative disease, epilepsy and trauma, the cell mounts a stress response with induction of a variety of proteins, most notably the 70 kD heat shock protein (Hsp70). The possibility that stress proteins might be neuroprotective was suspected because Hsp70, in particular, was induced to high levels in brain regions that were relatively resistant to injury. Hsp70 expression was also correlated with the phenomenon of induced tolerance. With the availability of transgenic animals and gene transfer, has it become increasingly clear that such heat shock proteins do indeed protect cells from injury. Several reports have now shown that selective overexpression of Hsp70 leads to protection in several different models of nervous system injury. This review will cover these studies, along with potential mechanisms by which Hsp70 might mediate cellular protection.