Regulation of alternative splicing of tau exon 10  

作　　者：Wei Qian Fei Liu 

机构地区：[1]Department of Biochemistry and Molecular Biology,School of Medicine, Nantong University [2]Jiangsu Key Laboratory of Neuroregeneration,School of Medicine, Nantong University [3]Department of Neurochemistry, Inge Grundke-Iqbal Research Floor,New York State Institute for Basic Research in Developmental Disabilities

出　　处：《Neuroscience Bulletin》2014年第2期367-377,共11页神经科学通报（英文版）

基　　金：supported by Nantong University;New York State Institute for Basic Research in Developmental Disabilities;by grants from the National Natural Science Foundation of China(81030059 and 81170317);the Basic Research Program of Education Department of Jiangsu Province,China(10KJA310040);the U.S.Alzheimer’s Association(Grant IIRG-10-173154);the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)of China

摘　　要：The neuronal microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in the brains of individuals with Alzheimer＇s disease and related neurodegenerative disorders. The adult human brain expresses six isoforms of tau generated by alternative splicing of exons 2, 3, and 10 of its pre-mRNA. Exon 10 encodes the second microtubule-binding repeat of tau. Its alternative splicing produces tau isoforms with either three or four microtubule-binding repeats, termed 3R-tau and 4R- tau. In the normal adult human brain, the level of 3R-tau is approximately equal to that of 4R-tau. Several silent and intronic mutations of the tau gene associated with FTDP-17T （frontotemporal dementia with Parkinsonism linked to chromosome 17 and specifically characterized by tau pathology） only disrupt exon 10 splicing, but do not influence the primary sequence of the tau protein. Thus, abnormal exon 10 splicing is sufficient to cause neurodegeneration and dementia. Here, we review the regulation of tau exon 10 splicing by cis-elements and trans-factors and summarize all the mutations associated with FTDP-17T and related tauopathies. The findings suggest that correction of exon 10 splicing may be a potential target for tau exon 10 splicing-related tauopathies.The neuronal microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in the brains of individuals with Alzheimer＇s disease and related neurodegenerative disorders. The adult human brain expresses six isoforms of tau generated by alternative splicing of exons 2, 3, and 10 of its pre-mRNA. Exon 10 encodes the second microtubule-binding repeat of tau. Its alternative splicing produces tau isoforms with either three or four microtubule-binding repeats, termed 3R-tau and 4R- tau. In the normal adult human brain, the level of 3R-tau is approximately equal to that of 4R-tau. Several silent and intronic mutations of the tau gene associated with FTDP-17T （frontotemporal dementia with Parkinsonism linked to chromosome 17 and specifically characterized by tau pathology） only disrupt exon 10 splicing, but do not influence the primary sequence of the tau protein. Thus, abnormal exon 10 splicing is sufficient to cause neurodegeneration and dementia. Here, we review the regulation of tau exon 10 splicing by cis-elements and trans-factors and summarize all the mutations associated with FTDP-17T and related tauopathies. The findings suggest that correction of exon 10 splicing may be a potential target for tau exon 10 splicing-related tauopathies.

关 键 词：alternative splicing TAU tau exon 10 TAUOPATHIES 

分 类 号：R749.16[医药卫生—神经病学与精神病学]