Fig. 1. The mechanism of heat-shock protein 70 (HSP70) production following focal ischemia in the brain. Ischemia produces denatured proteins within cells. The denatured proteins activate heat-shock factors (HSFs), perhaps by promoting dissociation of HSP90 from the HSFs. The HSFs are phosphorylated, form a trimer and bind to heat-shock elements (HSEs) on heat-shock genes, including Hsp70. This activates HSP70 transcription although HSP70 mRNA might not be synthesized in the infarct where ATP is limited. Outside the infarction HSP70 protein is synthesized in glia and neurons in a region defined as the ‘denatured protein’penumbra. HSP70, along with other chaperones, binds to denatured proteins to restore their structure and function and promotes survival of the glia and neurons. Abbreviation: P, phosphorylation.