The neuroprotective potential of heat shock protein 70 (HSP70).
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-kDa heat shock protein (HSP70). Whether stress proteins are neuroprotective has been hotly debated, as these proteins might be merely an epiphenomenon unrelated to cell survival. Only recently, with the availability of transgenic animals and gene transfer, has it become possible to overexpress the gene encoding HSP70 to test directly the hypothesis that stress proteins protect cells from injury. A few groups have now shown that overproduction of HSP70 leads to protection in several different models of nervous system injury. This review will cover these studies, along with the potential mechanisms by which HSP70 might mediate cellular protection.
Yenari
M A
MA
Departments of Neurosurgery, Neurology and Stanford Stroke Center, Stanford University Medical Center, Stanford University, Stanford, CA 94305, USA.
Giffard
R G
RG
Sapolsky
R M
RM
Steinberg
G K
GK
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000187:drug effects / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D011489:Protein Denaturation; D012333:RNA, Messenger / Q000378:metabolism; D020521:Stroke / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger