阿尔兹海默,Peli1,E3泛素连接酶 z-bo 2020-10-23 637

　　Recently, Xiao Yichuan's research group, a researcher at the Key Laboratory of Cancer and Microenvironment, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, published a research paper entitled Peli1 impairs microglial Aβ phagocytosis through promoting C/EBPβ degradation on PLOS Biology. The study revealed that E3 ubiquitin ligase (ie Peli1) directly mediates C/EBPβ ubiquitination modification and induces its degradation, thereby affecting a new mechanism of microglia's phagocytic function of amyloid-β (Aβ) , To provide new molecular targets for the pathological mechanism and clinical treatment of Alzheimer's Disease (AD).

　　AD is a common neurodegenerative disease. One of its characteristic pathological changes is that Aβ deposits in large amounts in the brain, causing neuronal death and cognitive impairment. In the central nervous system (Central Nervous System, CNS), the clearance of Aβ mainly depends on the phagocytosis of microglia. At present, the academic circles have not yet fully defined the molecular regulation mechanism that affects and regulates the phagocytic function of microglia.

　　Researchers have found in previous studies that Peli1 is specifically and highly expressed in microglia and mediates the occurrence and development of autoimmune neuroinflammation, Parkinson's Disease (PD) and viral encephalitis . This study further clarified the pathological mechanism of Peli1AD that negatively regulates the phagocytosis of Aβ by microglia, which makes the Aβ deposits in the brain unable to be cleared and causes the deterioration of AD. Studies have shown that Peli1 directly binds and mediates the ubiquitination and degradation of the transcription factor C/EBPβ. Since C/EBPβ is a key transcription factor for scavenger receptor CD36, the knockout of Peli1 promotes CD36 gene expression and enhances microglia Phagocytosis of Aβ by cells. Therefore, in the brains of the 5×FAD transgenic AD model mice lacking the Peli1 gene in the elderly, the clearance of Aβ by microglia was significantly enhanced and the deposition of Aβ in the brain was inhibited. In addition, the expression of Peli1 in the brain microglia of 5×FAD mice and the brain tissue of AD patients was significantly higher than that of normal controls, indicating that AD pathology can induce the expression of Peli1 in microglia. Therefore, Peli1 in microglia is a potential new molecular target for the diagnosis and treatment of AD.