Versatile cytoprotective activity of lipoic acid may reflect its ability to activate signalling intermediates that trigger the heat-shock and phase II responses

Although lipoic acid (LA) and its reduced derivative (DHLA) have broad antioxidant activity, it seems unlikely that this can adequately explain the remarkable neuroprotective effects of LA observed in rodents and in diabetic patients. It is proposed that this protection is mediated, in large measure, by induction of various protective proteins. More specifically, there is some reason to suspect that LA can trigger both heat-shock and phase II responses, and that LA may achieve this by catalyzing the formation of intramolecular disulfides in certain signalling proteins that funciton as detectors of oxidants and/or electrophiles. This hypothesis is readily testable, and, if true, would suggest that LA may have general utility for preventing or treating neurodegenerative disorders, and possibly also may retard the adverse impact of aging on brain function. This mode[ also predicts that LA should have anticarcinogenic activity. (C) 2001 Harcourt Publishers Ltd.