Inducible nitric oxide synthase and NFκB signaling in amyloid β-peptide induced neuron death and apoptosis
10.3760/cma.j.issn.1671-8925.2005.03.033
- VernacularTitle: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
- Author:
Yi YANG
1
;
En-Ming ZHANG
;
Xiao-Xiang ZHENG
Author Information
1. 浙江大学
- Keywords:
Nitric-oxide synthase;
NFκB;
Signal pathway;
Alzheimer's disease;
Apoptosis;
Necrosis
- From:
Chinese Journal of Neuromedicine
2005;4(3):295-302
- CountryChina
- Language:Chinese
-
Abstract:
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 responsecorrelative with expression ofiNOS, the activation of the NFκB signal pathway and the expression ofiNOS,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 Aβstimulation. 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.
