Abstract：
Alzheimer\'s disease (AD) and Parkinson\'s disease (PD) are the most common neurodegenerative disorders. Pathologically, AD and PD are characterized by the accumulation of misfolded proteins. Hence, they are also called as proteinopathy diseases. Gender is considered as one of the risk factors in both diseases. Estrogens are widely accepted to be neuroprotective in several neurodegenerative disorders. Estrogens can be produced in the central nervous system, where they are called as neurosteroids. Estrogens mediate their neuroprotective action mainly through their actions on estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). However, ERα is mainly involved in the growth and development of the primary and secondary sexual organs in females. Hence, the activation of ERα is associated with undesired side effects such as gynecomastia and increase in the risk of breast cancer, thromboembolism, and feminization. Therefore, selective activation of ERβ is often considered to be safer. In this review, we explore the role of ERβ in regulating the expression and functions of AD- and PD-associated genes. Additionally, we discuss the association of these genes with the amyloid-beta peptide (Aβ) and α-synuclein mediated toxicity. Ultimately, we established a correlation between the importance of ERβ activation and the process underlying ERβ\'s neuroprotective mechanisms in AD and PD.
摘要：
阿尔茨海默病(AD)和帕金森病(PD)是最常见的神经退行性疾病。病理上,AD和PD的特征在于错误折叠蛋白的积累。因此，它们也被称为蛋白质病。性别被认为是这两种疾病的危险因素之一。雌激素在几种神经退行性疾病中被广泛接受为神经保护。雌激素可以在中枢神经系统中产生，它们被称为神经类固醇。雌激素主要通过其对雌激素受体α（ERα）和雌激素受体β（ERβ）的作用来介导其神经保护作用。然而,ERα主要参与女性初级和第二性器官的生长发育。因此，ERα的激活与不良副作用有关，如男性乳房发育和乳腺癌风险的增加，血栓栓塞,女性化。因此,ERβ的选择性激活通常被认为是更安全的。在这次审查中,我们探讨了ERβ在调节AD和PD相关基因的表达和功能中的作用。此外,我们讨论了这些基因与淀粉样β肽（Aβ）和α-突触核蛋白介导的毒性的关联。最终,我们在AD和PD中建立了ERβ激活的重要性与ERβ神经保护机制的潜在过程之间的相关性。
