雌激素介导线粒体途径的神经保护作用研究  

Neuroprotective Effect of Estrogen-Mediated Mitochondrial Pathway

作　　者：戴月英 赵雨薇 姚思凡 沈丽霞 DAI Yue-ying;ZHAO Yu-wei;YAO Si-fan;SHEN Li-xia(Department of Pharmacy,Hebei North University,Zhangjiakou,075000,China)

机构地区：[1]河北北方学院药学系,中国张家口075000

出　　处：《神经药理学报》2021年第3期33-42,共10页Acta Neuropharmacologica

基　　金：河北省自然科学基金资助项目(No.H2019405057);河北省高等学校科学技术研究项目(No.ZD2020136);河北省研究生创新资助项目(No.CXZZSS2022145,No.CXZZSS2022151)。

摘　　要：阿尔茨海默病(Alzheimer’s disease,AD)是多因素引起的神经退行性疾病,以认知障碍、执行力障碍为主要的临床表现,发病机制有β淀粉样蛋白(β-amyloid,Aβ)级联和tau蛋白异常学说等。流行病学调查显示绝经后妇女较同龄男性AD发病率高1.5~3.0倍,认为与女性绝经后雌激素降低相关,并且研究表明雌激素有神经元保护作用,雌激素或直接或间接地影响线粒体。除此之外,由于线粒体被视为细胞的能量体、兴奋性毒性期间神经元生存力的关键调节剂,因而AD线粒体机制也成为AD发病机制的研究领域。Aβ可直接与线粒体膜结合,从而改变线粒体动力学和功能,导致能量代谢异常,最终引起细胞凋亡等一系列链式反应。研究表明线粒体功能障碍会加剧Aβ沉积和tau蛋白异常磷酸化,而这两种病理反过来又能促进线粒体损伤,通过线粒体依赖性凋亡通路来诱导细胞凋亡。该文就AD情况下,雌激素通过介导线粒体途径发挥神经保护作用作一综述,以期为AD防治提供一定的基础理论思路。Alzheimer’s disease(AD) is a multifactorial disease with cognitive and executive dysfunction as the main clinical manifestations. The pathogenesis of AD is Aβ cascade and abnormal tau protein,etc.. Epidemiological investigation showed that the incidence of AD in postmenopausal women was 1.5~3.0 times higher than that in men of the same age,estrogen either directly or indirectly affects mitochondria. In addition,because mitochondria are regarded as the energy body of cells and the key regulator of neuronal viability during excitotoxicity,the mitochondrial mechanism of AD has also become the research area of AD pathogenesis. Aβ can bind directly to the mitochondrial membrane,thus changing the dynamics and function of mitochondria,leading to abnormal energy metabolism,resulting in a series of chain reactions such as apoptosis. Studies have shown that mitochondrial dysfunction exacerbates Aβ deposition and tau abnormal phosphorylation,which in turn promotes mitochondrial injury and induces apoptosis through a mitochondrial dependent apoptotic pathway. This article reviews the neuroprotective effect of estrogen through mediating mitochondrial pathway in the case of AD,in order to provide some basic theoretical thinking for the prevention and treatment of AD.

关 键 词：阿尔茨海默病 雌激素 线粒体 神经保护作用 

分 类 号：R964[医药卫生—药理学]