Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer's disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors. Consequently, a deeper analysis of estrogen receptor (ER) expression and estrogen-metabolizing enzymes could interpret the importance of estrogen in age-linked cognitive alterations. Previous studies propose that hormone replacement therapy may attenuate AD onset in postmenopausal women, demonstrating that estrogen signaling is important for the development and progression of AD. For example, ERα exerts neuroprotection against AD by maintaining intracellular signaling cascades and study reported reduced expression of ERα in hippocampal neurons of AD patients. Similarly, reduced expression of ERβ in female AD patients has been associated with abnormal function in mitochondria and improved markers of oxidative stress. In this review, we discuss the critical interaction between estrogen signaling and AD. Moreover, we highlight the potential of targeting estrogen-related signaling for therapeutic intervention in AD.

中文翻译：

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阿尔茨海默氏病中的雌激素信号传导：阿尔茨海默氏痴呆症的分子研究和治疗靶点。

雌激素在大脑中起着至关重要的生理功能。然而，关于雌激素在阿尔茨海默氏病（AD）中的作用存在争论。女性在更年期前，更年期或更年期更容易发展为AD，这表明在AD发病机理中性别因素与雌激素信号传导减少有关。然而，雌激素介导的神经保护的潜在机制尚不清楚，并且由于存在雌激素相关因素而变得复杂。因此，对雌激素受体（ER）表达和雌激素代谢酶的更深入分析可以解释雌激素在与年龄相关的认知变化中的重要性。先前的研究表明，激素替代疗法可减轻绝经后女性的AD发作，证明雌激素信号通路对AD的发展和进程很重要。例如，ERα通过维持细胞内信号传导级联而对AD发挥神经保护作用，并且研究报道ERα在AD患者海马神经元中的表达减少。同样，女性AD患者中ERβ的表达减少与线粒体功能异常和氧化应激指标改善有关。在这篇综述中，我们讨论了雌激素信号传导与AD之间的关键相互作用。此外，我们强调了靶向雌激素相关信号转导用于AD的治疗干预的潜力。女性AD患者ERβ表达降低与线粒体功能异常和氧化应激指标改善有关。在这篇综述中，我们讨论了雌激素信号传导与AD之间的关键相互作用。此外，我们强调了靶向雌激素相关信号转导用于AD的治疗干预的潜力。女性AD患者ERβ表达降低与线粒体功能异常和氧化应激指标改善有关。在这篇综述中，我们讨论了雌激素信号传导与AD之间的关键相互作用。此外，我们强调了靶向雌激素相关信号转导用于AD的治疗干预的潜力。