Effects of oxidative stress and Alzheimer's amyloid-beta peptide on astrocytes

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Oxidative stress and deposition of amyloid-[beta] peptide (A[beta]) in brains have been hypothesized as causes of Alzheimer's disease (AD), and research into the effects of oxidative stress and A[beta] on cell functions should lead to better understanding of AD. Here we focused on these effects on astrocytes, since they are the major cell type which regulate and nurture neurons. We found that both oxidative stress and A[beta] activate two key signaling proteins in astrocytes, p38 mitogen-activated kinase and phospholipase A2. In turn, activation of these key proteins results in physical property changes of plasma membranes and in mitochondrial dysfunction. Mitochondrial dysfunction led to excess production of anionic superoxide, which may drive the disease development towards exacerbation of the oxidative and inflammatory conditions, characteristics of the AD brain. The findings derived from this study suggest that inhibitions of these key signaling proteins provide new therapeutic strategies to retard the progression of AD.