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 anti oxidant activity, it seems unlikely that this can adequately explain the re markable 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 res ponses, and that LA may achieve this by catalyzing the formation of intramo lecular disulfides in certain signalling proteins that funciton as detector s of oxidants and/or electrophiles. This hypothesis is readily testable, an d, if true, would suggest that LA may have general utility for preventing o r treating neurodegenerative disorders, and possibly also may retard the ad verse impact of aging on brain function. This mode[ also predicts that LA s hould have anticarcinogenic activity. (C) 2001 Harcourt Publishers Ltd.