Estradiol (E2) depletion increases nigral angiotensin system and inflammatory markers. Inhibition of nigral angiotensin mediates neuroprotection of E2 in Parkinson’s models. Astrocytes, neurons and microglia are involved in E2 regulation of nigral angiotensin. There is a critical period for the neuroprotective effects of E2 replacement therapy. Angiotensin receptor antagonists induce neuroprotection after the critical period.