Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, 171 77 Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
Essays Biochem. 2021 Dec 17;65(6):913-925. doi: 10.1042/EBC20200162.
The female sex hormone estrogen has been ascribed potent neuroprotective properties. It signals by binding and activating estrogen receptors that, depending on receptor subtype and upstream or downstream effectors, can mediate gene transcription and rapid non-genomic actions. In this way, estrogen receptors in the brain participate in modulating neural differentiation, proliferation, neuroinflammation, cholesterol metabolism, synaptic plasticity, and behavior. Circulating sex hormones decrease in the course of aging, more rapidly at menopause in women, and slower in men. This review will discuss what this drop entails in terms of modulating neuroprotection and resilience in the aging brain downstream of spatiotemporal estrogen receptor alpha (ERα) and beta (ERβ) signaling, as well as in terms of the sex differences observed in Alzheimer's disease (AD) and Parkinson's disease (PD). In addition, controversies related to ER expression in the brain will be discussed. Understanding the spatiotemporal signaling of sex hormones in the brain can lead to more personalized prevention strategies or therapies combating neurodegenerative diseases.
女性性激素雌激素被赋予了强大的神经保护特性。它通过与雌激素受体结合并激活雌激素受体来发出信号，根据受体亚型和上游或下游效应物，雌激素受体可以介导基因转录和快速非基因组作用。通过这种方式，大脑中的雌激素受体参与调节神经分化、增殖、神经炎症、胆固醇代谢、突触可塑性和行为。随着年龄的增长，循环性激素会减少，女性在绝经后减少得更快，男性减少得更慢。这篇综述将讨论时空雌激素受体α (ERα) 和β (ERβ) 信号下游调节衰老大脑中的神经保护和弹性方面，以及阿尔茨海默病 (AD) 和帕金森病 (PD) 中观察到的性别差异方面，这种减少意味着什么。此外，还将讨论与大脑中 ER 表达相关的争议。了解大脑中性激素的时空信号可以导致更个性化的预防策略或治疗神经退行性疾病的方法。
