Structure–nongenomic neuroprotection relationship of estrogens and estrogen-derived compounds

Nongenomic estrogen signaling pathways involve extranuclear estrogen receptors or function independently from estrogen receptors. These pathways participate in neuroprotection elicited by the hormone. Additional nongenomic neuroprotective effects are attributable to antioxidant and antiinflammatory actions of estrogens. Numerous chemical modifications to afford neuroprotective compounds from estrogens while eliminating estrogenicity and maintaining or enhancing nongenomic neuroprotection have been described. This review highlights recent structure–activity studies that revealed the importance of antioxidant effects for neuroprotective estrogen analogues and derivatives.