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β淀粉样蛋白(Aβ)通过核因子κB(NFκB)信号通路机制,促使诱导型一氧化氮合酶(iNOS)表达,最终导致神经元凋亡或坏死。在小胶质细胞和星形胶质细胞的协同作用下,产生了与iNOS表达相关的Aβ刺激的炎症反应、NFκB信号通路的活化,iNOS的表达,导致神经元过氧化亚硝酸盐损伤和阿尔茨海默病(AD)中神经的退行性损伤。微胶质细胞的CD36接受Aβ刺激后,与Src家族蛋白激酶成员Lyn结合。Lyn和Src家族另一成员Fyn一起,启动MAPK通路的信号应答,产生MCP-1和ROS等炎症因子。同时,Syk家族蛋白也参加了Aβ刺激促炎因子产生的信号传递。NFκB接受Aβ刺激后以独立于Src、Syk 的信号通道起作用。Aβ刺激微胶质细胞分泌的炎症因子诱导神经元细胞中iNOS的过量表达,产生过量过氧化亚硝酸盐,致使神经元损伤。
Amyloid beta (Aβ) induces the expression of inducible nitric oxide synthase (iNOS) through the nuclear factor kappa B (NFκB) signaling pathway, leading eventually to neuronal apoptosis or necrosis. Synergistic effects of microglia and astrocytes produce Aβ-stimulated inflammation associated with iNOS expression, activation of the NFκB signaling pathway, iNOS expression, leading to neuronal peroxynitrite damage and Alzheimer’s disease Degenerative nerve damage in Alzheimer’s disease (AD). CD36 of microglial cells, after being stimulated by Aβ, bind to Lyn, a member of the Src family of protein kinases. Together with Fyn, another member of the Src family, Lyn initiates the signal response of the MAPK pathway to produce inflammatory cytokines such as MCP-1 and ROS. In the meantime, Syk family proteins also participate in Aβ-stimulated proinflammatory cytokine signaling. NFκB acts on Aβ-independent signaling pathways independent of Src and Syk. A [beta] stimulates the secretion of inflammatory cytokines by glial cells, induces overexpression of iNOS in neuronal cells, produces excess nitrite and leads to neuronal damage.