Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review  

作　　者：Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu 

机构地区：[1]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products,Coinnovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [2]Department of Pharmacology,School of Pharmacy,Nantong University,Nantong,Jiangsu Province,China [3]Department of Biochemistry and Molecular Biology,School of Medicine,Nantong University,Nantong,Jiangsu Province,China [4]Department of Clinical Pharmacy,Affiliated Maternity and Child Health Care Hospital of Nantong University,Nantong University,Nantong,Jiangsu Province,China [5]Laboratory of Animal Center,Nantong University,Nantong,Jiangsu Province,China [6]Department of Neurochemistry,Inge Grundke-Iqbal Research Floor,New York State Institute for Basic Research in Developmental Disabilities,Staten Island,NY,USA

出　　处：《Neural Regeneration Research》2024年第6期1221-1232,共12页中国神经再生研究（英文版）

基　　金：supported by the Neural Regeneration Co-innovation Center of Jiangsu Province,Nantong University(to DC);the National Natural Science Foundation of China,Nos.81872853(to DC),81870941(to JHG);the Science and Technology Project of Nantong City,Nos.JC22022022(to FW)and JC2021059(to JM)。

摘　　要：Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

关 键 词：Alzheimer's disease cleavage site diagnosis MARKER neurofibrillary tangles PHOSPHORYLATION TAU Tau aggregation therapy TRUNCATION 

分 类 号：R749.16[医药卫生—神经病学与精神病学]