Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer's disease.
Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer's disease.
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DOI：
10.2174/156720511794604543
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发表时间：
2011-01
影响因子：
2.1
通讯作者：
Chuanyu Li;Rui Zhao;K. Gao;Zheng Zachory Wei;Michael Yaoyao Yin;L. Lau;D. Chui;A. Yu
中科院分区：
文献类型：
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作者：
Chuanyu Li;Rui Zhao;K. Gao;Zheng Zachory Wei;Michael Yaoyao Yin;L. Lau;D. Chui;A. Yu
阿尔茨海默病（AD）是一种神经退行性疾病，其主要临床特征为记忆丧失、痴呆和认知障碍。神经炎症参与几种神经退行性疾病的发作。星形胶质细胞是中枢神经系统（CNS）中最丰富的胶质细胞类型，并且似乎参与神经炎症的诱导。在应激和损伤下，星形胶质细胞变成星形胶质细胞，导致促炎细胞因子和趋化因子的表达上调，这与AD的发病机制相关。细胞因子及其相关分子在中枢神经系统的神经保护和神经退行性变中发挥作用。在AD早期发病过程中，淀粉样蛋白β（Aβ）、S100 B和IL-1β可导致星形胶质细胞和神经元之间Aβ生成的恶性循环，导致慢性、持续和进行性的神经炎症。在AD的晚期阶段，已显示从星形胶质细胞分泌的TRAIL与神经元上的死亡受体5（DR 5）结合，以半胱天冬酶-8依赖性方式触发细胞凋亡。TGFβ1可激活星形胶质细胞产生更多的Aβ，使星形胶质细胞增生加重。TGFβ2还可与Aβ协同作用，破坏神经元内溶酶体的稳定性，导致神经元死亡。炎症分子可以是用于诊断的潜在生物标志物或用于治疗干预的靶分子。了解它们的作用及其与活化星形胶质细胞的关系对于减轻AD早期的神经炎症尤为重要。本文就星形胶质细胞在AD神经炎症发病机制中的作用作一综述。
Alzheimer's disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B and IL-1β could bring about a vicious cycle of Aβ generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGFβ1 to generate more Aβ and to undergo the aggravating astrogliosis. TGFβ2 was also observed to cooperate with Aβ to cause neuronal demise by destroying the stability of lysosomes in neurons. Inflammatory molecules can be either potential biomarkers for diagnosis or target molecules for therapeutic intervention. Understanding their roles and their relationship with activated astrocytes is particularly important for attenuating neuroinflammation in the early stage of AD. The main purpose of this review is to provide a comprehensive insight into the role of astrocytes in the neuroinflammatory pathogenesis of AD.