Altered O-GlcNAcylation and mitochondrial dysfunction, a molecular link between brain glucose dysregulation and sporadic Alzheimer 's disease
Chia-Wei Huang1
Nicholas C.Rust1
Hsueh-Fu Wu2
Gerald W.Hart1
1.Complex Carbohydrate Research Center,University of Georgia,Athens,GA,USA;Department of Biochemistry and Molecular Biology,University of Georgia,Athens,GA,USA2.Department of Biochemistry and Molecular Biology,University of Georgia,Athens,GA,USA;Center for Molecular Medicine,University of Georgia,Athens,GA,USA
摘要：Alzheimer's disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021, with this number expected to double in the next 40 years without any sort of treatment. Due to its heterogeneity and complexity, the etiology of Alzheimer's disease, especially sporadic Alzheimer's disease, remains largely unclear. Compelling evidence suggests that brain glucose hypometabolism, preceding Alzheimer's disease hallmarks, is involved in the pathogenesis of Alzheimer's disease. Herein, we discuss the potential causes of reduced glucose uptake and the mechanisms underlying glucose hypometabolism and Alzheimer's disease pathology. Specifically, decreased O-GlcNAcylation levels by glucose deficiency alter mitochondrial functions and together contribute to Alzheimer's disease pathogenesis. One major problem with Alzheimer's disease research is that the disease progresses for several years before the onset of any symptoms, suggesting the critical need for appropriate models to study the molecular changes in the early phase of Alzheimer's disease progression. Therefore, this review also discusses current available sporadic Alzheimer's disease models induced by metabolic abnormalities and provides novel directions for establishing a human neuronal sporadic Alzheimer's disease model that better represents human sporadic Alzheimer's disease as a metabolic disease.
机标关键词：alzheimermolecularglucosebetweenbrainlinkaltereddisease
论文发表日期：2023-04-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：5( 779-783 )
英文信息