Menopause and Parkinson's disease. Interaction between estrogens and brain renin-angiotensin system in dopaminergic degeneration

The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease (PD) have not yet been clarified, and it is controversial whether there is a critical period for neuroprotection. Studies in animal models and clinical and epidemiological studies indicate that estrogens induce dopaminergic neuroprotection. Recent studies suggest that inhibition of the brain renin-angiotensin system (RAS) mediates the effects of estrogens in PD models. In the substantia nigra, ovariectomy induces a decrease in levels of estrogen receptor-alpha (ER-alpha) and increases angiotensin activity, NADPH-oxidase activity and expression of neuroinflammatory markers, which are regulated by estrogen replacement therapy. There is a critical period for the neuroprotective effect of estrogen replacement therapy, and local ER-alpha and RAS play a major role. Astrocytes play a major role in ER -alpha-induced regulation of local RAS, but neurons and microglia are also involved. Interestingly, treatment with angiotensin receptor antagonists after the critical period induced neuroprotection. (C) 2016 Elsevier Inc. All rights reserved.