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

Abstract 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-α (ER-α) 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-α and RAS play a major role. Astrocytes play a major role in ER-α-induced regulation of local RAS, but neurons and microglia are also involved. Interestingly, treatment with angiotensin receptor antagonists after the critical period induced neuroprotection.