阿尔茨海默病与神经炎症:TNF-α的调控作用

Neuroinflammation in Alzheimer’s Disease:the Regulatory Effects of TNF-α

阿尔茨海默病(AD)是一种神经退行性疾病,其相关病变包括淀粉样蛋白β在脑内沉积形成老年斑、过度磷酸化的Tau蛋白在神经细胞内聚集形成的神经原纤维缠结、轴突变性等。越来越多的证据表明,AD的发病机制并不局限于神经元,也与脑组织的神经胶质细胞密切相关。神经胶质细胞中的小胶质细胞和星型胶质细胞在神经炎症过程中发挥多方面的作用,因此影响AD病理变化的发生、发展和转归。小胶质细胞和星型胶质细胞在神经炎症过程中分泌众多细胞因子和趋化因子,其中TNF-α可特异性结合细胞表面受体TNF-R1和TNF-R2,激活NF-κB、JNK(cJun)等信号通路,促进更多炎症细胞因子的表达,参与炎症诱导、细胞凋亡、APP和Tau蛋白的生成等病理过程。该文拟对神经胶质细胞及TNF-α调控神经炎症在阿尔茨海默病中的作用及机制进行综述。

AD(Alzheimer’s disease)is a neurodegenerative disease,its pathogenesis involves amy­loidβdeposition leading to senile plaques in the brain,overphosphorylated Tau protein accumulates in nerve cells to form neurofibrillary tangles,axonal degeneration,etc.There is growing evidence,however,show­ing the pathogenesis of AD is not limited to neurons,but is also closely related to glial cells in brain tissue.Indeed,microglia and astrocytes play multiple roles in the neuroinflammatory process thus influencing the onset,development,and outcome of AD.Microglia and astrocytes secrete many cytokines and chemokines in the process of neuroinflammation,among which TNF-a specifically binds to the cell surface receptors TNF-R1 and TNF-R2,followed by the activation of NF-кВ,JNK(c-Jun)and other signaling pathways promoting the expression of more inflammatory cytokines,what’s more,impacting multiple pathological processes such as inflammation induction,apoptosis,APРand Tau protein production.This paper aims to review the role and mechanism of glial cells and TNF-a in regulating neuroinflammation in AD.