alpha-lipoic acid protects rat cortical neurons against cell death inducedby amyloid and hydrogen peroxide through the Akt signalling pathway

Substantial evidence suggests that the accumulation of beta -amyloid (A bet a)-derived peptides contributes to the aetiology of Alzheimer's disease (AD ) by stimulating formation of free radicals. Thus, the antioxidant alpha -l ipoate, which is able to cross the blood-brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effec tiveness of alpha -lipoic acid (LA) against cytotoxicity induced by A beta peptide (31-35) (30 muM) and hydrogen peroxide (H2O2) (100 muM) with the ce llular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons o f rat cerebral cortex. We found that treatment with LA protected cortical n eurons against cytotoxicity induced by A beta or H2O2. In addition, LA-indu ced increase in the level of Akt in the neurons was observed by Western blo t. The LA-induced neuroprotection and Akt increase were attenuated by pretr eatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 muM) . Our data suggest that the neuroprotective effects of the antioxidant LA a re partly mediated through activation of the PKB/Akt signaling pathway. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.