Xiaofeng LiChongqing Medical University, China
Title: Decreased expression of protein O-linked mannose ? 1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer’s disease-like pathologies
Alzheimer’s disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of ?-amyloid peptide (A?) and tau hyperphosphorylation, respectively. Mannosylation, a particular type of post-translational modification, may be involved in the pathogenesis of AD. However, its underlying mechanism remains unclear. Protein O-linked mannose ? 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine ?-1,2-Man linkage of O-mannosylglycan, which can increase the protein post-translational mannosylation level. The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. In this study, the expression of POMGnT1 was measured in AD models [?-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. Additionally, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. POMGnT1 overexpression may lower A? levels by reducing APP production and downregulating ?-and ?-secretase activities. It also promoted clearance of A? by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. Hence, it was concluded that POMGnT1 was involved in the pathogenic process of AD. The decreased expression of POMGnT1 contributes to AD-like pathologies.
Xiaofeng Li has completed her PHD at the age of 33 years from Chongqing Medical University, China. She is the vice-head of Neurology department of second hospital affiliated to Chongqing Medical University, China. She has over 50 publications. She has been serving as a peer reviewer of several reputed journals.