The Antioxidant Vitamin E Modulates Amyloid B-Peptide- Induced Creatine Kinase Activity Inhibition and Increased Protein Oxidation: Implications for the Free Radical Hypothesis of Alzheimer's Disease
نویسندگان
چکیده
Amyloid B-peptide (AB), the main constituent of senile plaques in Alzheimer's disease (AD) brain, is hypothesized to be a key factor in the neurodegeneration seen in AD. Recently it has been shown by us and others that the neurotoxicity of AB occurs in conjunction with free radical oxidative stress associated with the peptide. AB(1-40) and several other fragments of the AB sequence are associated with free radicals in solution that are detectable using electron paramagnetic resonance spectroscopy. These free radicals were shown to attack brain cell membranes, initiate lipid peroxidation, increase Ca influx and damage membrane and cytosolic proteins. In AD brain obtained under rapid autopsy protocol, the activity of the oxidatively-sensitive enzyme creatine kinase was shown to be significantly reduced. We reasoned that AB-associated free radical-induced modification of creatine kinase activity and other markers of cellular damage might be modulated by free radical scavengers. Accordingly, this study demonstrates that vitamin E can modulate AB(25-35)induced oxidative damage to creatine kinase and cellular proteins in cultured embryonic hippocampal neurons. These results, consistent with the hypothesis of free radical-mediated AB toxicity in AD, are discussed with deference to potential free radical scavengers as therapeutic agents for slowing the progression of AD.
منابع مشابه
Vitamin E Prevents Alzheimer's Amyloid beta-Peptide (1-42)-Induced Neuronal Protein Oxidation and Reactive Oxygen Species Production.
Amyloid beta-peptide (Abeta) is a 42-43 amino acid peptide known to accumulate in Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity caused by Abeta is a result of its associated free radicals, which can play an important role in generating oxidative stress. Abeta(25-35)-associated oxidative stress-induced neuronal death in vitro is well established by many laboratori...
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