β淀粉样蛋白诱导神经元坏死和调亡中的诱导型一氧化氮合酶和NFκB信号通路(英文)

Inducible nitric oxide synthase and NFκB signaling in amyloid β-peptide induced neuron death and apoptosis

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 β-peptide (Aβ) stimulating inducible nitric oxide synthase (iNOS) induces neuron death or apoptosis through the transcription factor NFκB (nuclear factor κB) signal pathway mechanism. Aβ functiones together with microglia and astrocyte to stimulate the inflammatory response correlative with expression of iNOS, the activation of the NFκB signal pathway and the expression of iNOS, which results in significant peroxynitrite damage to neurons and the neurodegeneration in Alzheimer's disease (AD). Activation of CD36 signaling in microgila by Aβ fibrils initiates the association of the Src-family kinase Lyn with CD36. Together with another Src kinase, Fyn, Lyn activates a MAPK signaling response and results in the activation of inflammatory programs such as the production of MCP-1 and ROS. In parallel, Syk-family kinase activity specifically regulates increased cytokine production in response to Aβ stimulation. After the stimulation, NFκB works independent of Src and Syk activation. Aβ-stimulated microglial secretes TNF-α and O2-, resulting in iNOS overexpression and excessive peroxynitrite and neuronal apoptosis.