Protective Effects of Vitamin E against Oxidative Damage Induced by Aβ_1–40Cu(II) Complexes

β-amyloid peptide (A(3) is considered to be responsible for the formation of senile plaques, which is the hallmark of Alzheimer's disease (AD). Oxidative stress, manifested by protein oxidation and lipid peroxidation, among other alterations, is a characteristic of AD brain. A growing body of evidence has been presented in support of Ap_1–40 forming an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. Aβ_1–40Cu(II) complexes generate neurotoxic hydrogen peroxide (H₂O₂) from O₂ via Cu²⁺ reduction, though the precise reaction mechanism is unclear. The toxicity of Ap_1–40 or the Ap_1–40Cu(II) complexes to cultured primary cortical neurons was partially attenuated when (+)-α-tocopherol (vitamin E) as free radical antioxidant was added at a concentration of 100 μM. The data derived from lactate dehydrogenase (LDH) release and the formation of H₂O₂ confirmed the results from the MTT assay. These findings indicate that copper binding to Aβ_1–40 can give rise to greater production of H₂O₂, which leads to a breakdown in the integrity of the plasma membrane and subsequent neuronal death. Groups treated with vitamin E exhibited much slighter damage, suggesting that vitamin E plays a key role in protecting neuronal cells from dysfunction or death.

Edited by Liqin ZHAO