Understanding Tau pathology:Insights from animal modelsOACSCDCSTPCD
Tauopathies represent a class of neurodegenerative diseases(NDs),including Alzheimer’s disease(AD),progressive supranuclear palsy(PSP),Pick’s disease(PiD),and corticobasal degeneration(CBD),defined by intracellular accumulation of misfolded and hyperphosphorylated tau protein.The pathogenic cascade involves hyperphosphorylation,conformational changes,and aggregation into neurofibrillary tangles(NFTs),which are spatially and functionally linked to neuronal dysfunction,synaptic loss,and progressive cognitive and motor decline.To elucidate tau-mediated mechanisms,diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated.Although these models have advanced understanding of tau aggregation and propagation,tau-targeting therapies have failed to produce clinical benefits,raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets.This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate(NHP)tauopathy models,highlighting mechanistic insights into tau-driven pathology.The advantages,limitations,and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.
Han Zhang;Ming-Tian Pan;Yu-Xuan Li;Xiao-Jiang Li;Xiang-Yu Guo;Da-Jian He
Guangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Brain Research Centre,Department of Neurobiology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,Guangdong 518055,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Lingang Laboratory,Shanghai 200031,China Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangdong Key Laboratory of Non-human Primate Research,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangdong Key Laboratory of Non-human Primate Research,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Lingang Laboratory,Shanghai 200031,China Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangdong Key Laboratory of Non-human Primate Research,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangdong Key Laboratory of Non-human Primate Research,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China Lingang Laboratory,Shanghai 200031,China Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangdong Key Laboratory of Non-human Primate Research,Guangzhou,Guangdong 510632,China
医药卫生
TauopathyMouse modelMonkey modelPathogenesisNon-human primates
《Zoological Research》 2025 (5)
P.1244-1258,15
supported by the National Key Research and Development Program of China(2021YFF0702201,2021YFF0702204)Natural Science Foundation of Guangdong Province(2022A1515012651)。
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