星形胶质细胞在阿尔茨海默病中的功能变化及分子机制

Pathological Roles and Mechanisms of Astrocytes in Alzheimer's Disease

星形胶质细胞在脑内数量最多,分布最广,对神经元有营养支持的作用,并且能够调控神经元的活性。越来越多的证据表明星形胶质细胞激活参与阿尔茨海默病(Alzheimer's disease,AD)的发生和发展。在AD病理情况下,星形胶质细胞在多种因子如β淀粉样蛋白(beta-amyloid,Aβ)和促炎细胞因子的作用下被激活,激活的星形胶质细胞进一步释放一氧化氮(Nitric oxide,NO)和多种炎性因子增强炎症级联反应。功能失常的星形胶质细胞会促进Aβ的产生,减弱对Aβ的摄取和清除,导致Aβ聚集沉积形成老年斑。激活的星形胶质细胞释放的炎症因子还能显著增加神经元内tau蛋白的异常过度磷酸化,产生神经纤维缠结。本文对星形胶质细胞在AD中参与神经变性的功能变化和分子机制进行总结,为星形胶质细胞作为靶点预防及治疗AD提供一定的理论依据。

Astrocytes, as the most abundant and widely distributed neuroglial cells in the brain, play a critical role in providing trophic support to neurons and regulating the activities of neurons. Accumulating evidence suggests that activated astrocytes are involved in the pathophysiology of Alzheimer＇s disease（AD）. In AD pathological conditions, a variety of factors, including beta-amyloid（Aβ） and many proinflammatory cytokines, may activate astrocytes. Reactive astrocytes in turn produce nitric oxide（NO） and proinflammatory cytokines that contribute to a reinforced inflammatory cascade. Dysfunctional astrocytes is characterized with increased Aβ production,reduced Aβ uptake and clearance, leading to Aβ aggregation and formation of senile plaques. Moreover, reactive astrocytes-derived inflammatory cytokines may significantly induce tau hyperphosphorylation, which leads to the appearance of intraneuronal neurofibrillary tangles. In this review, the pathological functions of astrocytes in neurodegeneration and the underlying molecular mechanisms were summarized in an attempt to provide theoretical foundation as well as strategies for the prevention and treatment of AD.