C/EBPβ/AEP 信号通路驱动阿尔茨海默病发病机制。
C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis.
机构信息
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology (SIAT), Shenzhen, 518034, China.
出版信息
Neurosci Bull. 2023 Jul;39(7):1173-1185. doi: 10.1007/s12264-023-01025-w. Epub 2023 Feb 3.
Abstract
Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.
摘要
阿尔茨海默病（AD）是最常见的痴呆症类型。几乎三分之二的 AD 患者为女性。女性对 AD 发病的更高易感性的原因尚不清楚。然而，众所周知，绝经过渡期间的激素变化与 AD 有关。最近，我们报道卵泡刺激素（FSH）通过激活 CCAAT 增强子结合蛋白（C/EBPβ）/天冬酰胺内肽酶（AEP）途径促进 AD 病理学并增强认知功能障碍。这篇综述总结了我们目前对 C/EBPβ/AEP 途径通过切割包括 APP 和 Tau 在内的多种关键 AD 分子在驱动 AD 发病机制中的关键作用的理解，解释了 FSH 在增加绝经后女性 AD 易感性中的作用和机制。FSH-C/EBPβ/AEP 途径可能成为治疗 AD 的新的治疗靶点。
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