Pii: S0304-3940(01)02205-4

Substantial evidence suggests that the accumulation of b-amyloid (Ab)-derived peptides contributes to the aetiology of Alzheimer’s disease (AD) by stimulating formation of free radicals. Thus, the antioxidant a-lipoate, which is able to cross the blood–brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effectiveness of a-lipoic acid (LA) against cytotoxicity induced by Ab peptide (31–35) (30 mM) and hydrogen peroxide (H2O2) (100 mM) with the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons of rat cerebral cortex. We found that treatment with LA protected cortical neurons against cytotoxicity induced by Ab or H2O2. In addition, LA-induced increase in the level of Akt in the neurons was observed by Western blot. The LA-induced neuroprotection and Akt increase were attenuated by pretreatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 mM). Our data suggest that the neuroprotective effects of the antioxidant LA are partly mediated through activation of the PKB/Akt signaling pathway. q 2001 Elsevier Science Ireland Ltd. All rights reserved.