In many of the studies cited above using diverse cell types and cytotoxic insults, naturally occurring 17β-estradiol (17β-E2) and its diastereomer, 17α-estradiol (17α-E2), which is almost inactive as a hormone, have been found to be equally neuroprotective. Similarly, studies with a variety of novel estrogen analogues have confirmed that the structure–activity relationship for neuroprotection with this class of compounds differs significantly from the structural requirements for ER-dependent gene transcription [55–59]. For example, the complete enantiomer of 17β-E2 (ent-17β-E2) has identical physiochemical properties as 17β-E2 except for interactions with other stereospecific molecules such as ERs. Ent-17β-E2 is reported to interact only weakly with uterine-derived ERs [60,61] and lacks estrogenic effects on reproductive tissues in rodents [62,63].
In many of the studies cited above using diverse cell types and cytotoxic insults, naturally occurring 17β-estradiol (17β-E2) and its diastereomer, 17α-estradiol (17α-E2), which is almost inactive as a hormone, have been found to be equally neuroprotective. Similarly, studies with a variety of novel estrogen analogues have confirmed that the structure–activity relationship for neuroprotection with this class of compounds differs significantly from the structural requirements for ER-dependent gene transcription [55–59]. For example, the complete enantiomer of 17β-E2 (ent-17β-E2) has identical physiochemical properties as 17β-E2 except for interactions with other stereospecific molecules such as ERs. Ent-17β-E2 is reported to interact only weakly with uterine-derived ERs [60,61] and lacks estrogenic effects on reproductive tissues in rodents [62,63].
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