Figure 2.

Schematic model illustrating the ERβ-dependent E2-induced neuroprotection against oxidative stress. Exposure to oxidative stress induces cytochrome c (cyt c) release into the cytoplasm. Once in the cytosol cyt c mediates the activation of the adaptor molecule apoptosis–protease activating factor-1 (Apaf-1), generating the apoptosome. Apoptosome can recruit caspase-9 favoring proteinase activation. These events induce the catalytic maturation of caspase-3, which mediates the biochemical and morphological features of apoptosis. E2, via the synergy between extranuclear and nuclear ERβ activities, increases neuroglobin (Ngb) levels, reallocates Ngb at mitochondria, facilitates Ngb-cytochrome c interaction, and prevents apoptosome formation. For details, see text.