Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy  

作　　者：Jinwang Ye Huali Wan Sihua Chen Gong-Ping Liu 

机构地区：[1]Shenzhen Key Laboratory of Marine Biotechnology and Ecology,College of Life Sciences and Oceanography,Shenzhen University,Shenzhen,Guangdong Province,China [2]Department of Laboratory Medicine,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong Province,China [3]Co-innovation Center of Neurodegeneration,Nantong University,Nantong,Jiangsu Province,China [4]Department of Pathophysiology,School of Basic Medicine and the Collaborative Innovation Center for Brain Science,Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei Province,China

出　　处：《Neural Regeneration Research》2024年第7期1489-1498,共10页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82101493(to JY)。

摘　　要：Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关 键 词：ACETYLATION Alzheimer’s disease cognitive deficits GLIOSIS mitochondria damage NEUROINFLAMMATION phosphorylation synaptic impairments TAU tau immunotherapy 

分 类 号：R749.16[医药卫生—神经病学与精神病学]