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

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 Aβ neurotoxicity 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 Aβ clearance, 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.

CSTR: 32200.14.cjcb.2021.10.0013