Affiliations: [a] Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, USA | [b] Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA | [c] Current address: ERPRC/Neurochemistry, Harvard Medical School, Southborough, USA
Correspondence:
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Corresponding author: D. Allan Butterfield, Department of Chemistry, Center of Membrane Sciences and Sanders-Brown Center on Aging, 121 Chemistry-Physics Bldg., University of Kentucky, Lexington, Kentucky 40506-0055, USA, Tel.: +1 606 257 3184, Fax: +1 606 257 5876, E-mail: [email protected]
Abstract: Amyloid ß-peptide (Aß) is a 42-43 amino acid peptide known to accumulate in Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity caused by Aß is a result of its associated free radicals, which can play an important role in generating oxidative stress. Aß(25-35)-associated oxidative stress-induced neuronal death in vitro is well established by many laboratories, including ours. However, the oxidative stress-induced by the full-length [Aß(1-42)] peptide is not well investigated. The protective effect of antioxidant vitamin E in full-length peptide-induced oxidative stress also has not been reported. Here, we report that the increased protein oxidation, reactive oxygen species (ROS) formation, and neurotoxicity induced by Aß(1-42) in primary rat embryonic hippocampal neuronal culture are prevented by the free radical scavenger and antioxidant vitamin E. To test the hypothesis that vitamin E's protective effect may be due to inhibition of fibril formation, electron microscopy studies were undertaken. Vitamin E does not inhibit Aß(1-42) fibril formation, suggesting that the neuroprotection afforded by this molecule stems from other processes, most probably through the scavenging of Aß-associated free radicals. These results may have implications on the treatment of Alzheimer's disease.
