Journal
FRONTIERS IN NEUROENDOCRINOLOGY
Volume 29, Issue 4, Pages 463-475Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yfrne.2007.12.005
Keywords
estrogen; oxidative stress; neurodegeneration; Alzheimer's disease; neuroprotection; mitochondria; calcium; catecholestrogen; aging; reactive oxygen species
Categories
Ask authors/readers for more resources
Estradiol is a potent preventative against neurodegenerative disease, in part, by activating antioxidant defense systems scavenging reactive oxygen species, limiting mitochondrial protein damage, improving electron transport chain activity and reducing mitochondrial DNA damage. Estradiol also increases the activity of complex IV of the electron transport chain, improving mitochondrial respiration and ATP production under normal and stressful conditions. However, the high oxidative cellular environment present during neurodegeneration makes estradiol a poor agent for treatment of existing disease. Oxidative stress stimulates the production of the hydroperoxide-dependent hydroxylation of estradiol to the catecholestrogen metabolites, which can undergo reactive oxygen species producing redox cycling, setting up a self-generating toxic cascade offsetting any anti oxidant/antiapoptotic effects generated by the parent estradiol. Additional disease-induced factors can further perpetuate this cycle. For example dysregulation of the catecholamine system could alter catechol-O-methyltransferase-catalyzed methylation, preventing removal of redox cycling catecholestrogens from the system enhancing pro-oxidant effects of estradiol. (C) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available