阿尔茨海默病中内质网应激与胶质细胞介导的神经炎症之间的联系

Associations between Endoplasmic Reticulum Stress and Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

阿尔茨海默病(Alzheimer’s disease,AD)是一种进行性的、与年龄相关的神经退行性疾病。科学界普遍认为,AD的主要致病因素是在海马及皮层中异常沉积的β-淀粉样蛋白(β-amyloid,Aβ)斑块扩散到整个脑部,并产生严重的神经毒性作用,最终导致突触丢失和神经元死亡,这些病理特征是导致记忆障碍的神经基础。然而,斑块导致毒性的潜在机制仍不清楚。越来越多的证据表明,内质网应激(endoplasmic reticulum stress,ERS)参与AD的病理发展,包括抑制Aβ的清除、减少突触传递及诱导神经元细胞损伤等,而ERS所激活的未折叠蛋白反应(unfolded?protein response,UPR)三条途径都可引发促炎信号并促使胶质细胞活化,过度激活的胶质细胞进而诱导神经元发生炎症反应,加剧AD病理。因此,内质网应激和胶质细胞介导的神经炎症之间存在偶联,对AD病理有明显的影响。该综述将阐述在AD病理中,内质网应激与胶质细胞介导的神经炎症之间的联系。

As a progressive,age-related neurodegenerative disease,the major pathogenic factor of AD(Alzheimer’s disease)is the abnormal deposition of Aβ(β-amyloid)plaques in the hippocampus and cortex,which spread throughout the brain and shows severe neurotoxic effects leading to memory impairment,synaptic loss and neuronal death.However,the potential mechanism of Aβneurotoxicity has not been elucidated.An increasing body of evidence revealed that ERS(endoplasmic reticulum stress)is involved in the pathological development of AD,including inhibition of Aβclearance,reduction of synaptic transmission and induction of neuronal damage.Three UPR(unfolded?protein response)pathways activated by ERS can generate pro-inflammatory signals and promote glial activation.Overactivated glial cells induce neuronal inflammatory response and exacerbate AD pathology.Therefore,there is a coupling between ERS and neuroinflammation,which has a significant impact on Alzheimer’s disease.This review describes the relationship between ERS and glial cells-mediated neuroinflammation in AD pathology.