· neuron migration · apoptotic process · cellular component disassembly involved in execution phase of apoptosis · axonogenesis · adult walking behavior · axon cargo transport · regulation of autophagy · regulation of microtubule polymerization · positive regulation of microtubule polymerization · negative regulation of intracellular transport · positive regulation of axon extension · mitochondrion transport along microtubule · generation of neurons
^Shin RW, Iwaki T, Kitamoto T, Tateishi J. Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab. Invest. May 1991, 64 (5): 693–702. PMID 1903170.
^Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. U.S.A. June 1988, 85 (11): 4051–5. PMC 280359. PMID 3131773. doi:10.1073/pnas.85.11.4051.
^Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. October 1989, 3 (4): 519–26. PMID 2484340. doi:10.1016/0896-6273(89)90210-9.
^Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. U.S.A. May 1975, 72 (5): 1858–62. PMC 432646. PMID 1057175. doi:10.1073/pnas.72.5.1858.
^Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, Sato-Yoshitake R, Takei Y, Noda T, Hirokawa N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. June 1994, 369 (6480): 488–91. PMID 8202139. doi:10.1038/369488a0.
^Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. U.S.A. June 2001, 98 (12): 6923–8. PMC 34454. PMID 11381127. doi:10.1073/pnas.121119298.
进一步阅读
Goedert M, Crowther RA, Garner CC. Molecular characterization of microtubule-associated proteins tau and MAP2. Trends Neurosci. 1991, 14 (5): 193–9. PMID 1713721. doi:10.1016/0166-2236(91)90105-4.
Morishima-Kawashima M, Hasegawa M, Takio K; et al. Hyperphosphorylation of tau in PHF. Neurobiol. Aging. 1995, 16 (3): 365–71; discussion 371–80. PMID 7566346. doi:10.1016/0197-4580(95)00027-C. 引文格式1维护：显式使用等标签 (link)
Goedert M, Spillantini MG. Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease. Biochim. Biophys. Acta. 2000, 1502 (1): 110–21. PMID 10899436. doi:10.1016/S0925-4439(00)00037-5.
Morishima-Kawashima M, Ihara Y. [Recent advances in Alzheimer's disease]. Seikagaku. 2002, 73 (11): 1297–307. PMID 11831025.
Blennow K, Vanmechelen E, Hampel H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Mol. Neurobiol. 2002, 24 (1–3): 87–97. PMID 11831556. doi:10.1385/MN:24:1-3:087.
Ingram EM, Spillantini MG. Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends in molecular medicine. 2003, 8 (12): 555–62. PMID 12470988. doi:10.1016/S1471-4914(02)02440-1.
Pickering-Brown S. The tau gene locus and frontotemporal dementia. Dementia and geriatric cognitive disorders. 2004, 17 (4): 258–60. PMID 15178931. doi:10.1159/000077149.
van Swieten JC, Rosso SM, van Herpen E; et al. Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17. Dementia and geriatric cognitive disorders. 2004, 17 (4): 261–4. PMID 15178932. doi:10.1159/000077150. 引文格式1维护：显式使用等标签 (link)
Kowalska A, Jamrozik Z, Kwieciński H. Progressive supranuclear palsy--parkinsonian disorder with tau pathology. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. 2004, 42 (2): 119–23. PMID 15266787.
Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum. Mutat. 2005, 24 (4): 277–95. PMID 15365985. doi:10.1002/humu.20086.
Lee HG, Perry G, Moreira PI; et al. Tau phosphorylation in Alzheimer's disease: pathogen or protector?. Trends in molecular medicine. 2005, 11 (4): 164–9. PMID 15823754. doi:10.1016/j.molmed.2005.02.008. 引文格式1维护：显式使用等标签 (link)
Hardy J, Pittman A, Myers A; et al. Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens. Biochem. Soc. Trans. 2005, 33 (Pt 4): 582–5. PMID 16042549. doi:10.1042/BST0330582. 引文格式1维护：显式使用等标签 (link)
Deutsch SI, Rosse RB, Lakshman RM. Dysregulation of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer's disease, frontotemporal dementia and schizophrenia with therapeutic implications. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2007, 30 (8): 1369–80. PMID 16793187. doi:10.1016/j.pnpbp.2006.04.007.
Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Internal medicine journal. 2006, 36 (10): 652–60. PMID 16958643. doi:10.1111/j.1445-5994.2006.01153.x.
Pittman AM, Fung HC, de Silva R. Untangling the tau gene association with neurodegenerative disorders. Hum. Mol. Genet. 15. 2006,. Spec No 2 (Review Issue 2): R188–95. PMID 16987883. doi:10.1093/hmg/ddl190.
Roder HM, Hutton ML. Microtubule-associated protein tau as a therapeutic target in neurodegenerative disease. Expert Opin. Ther. Targets. 2007, 11 (4): 435–42. PMID 17373874. doi:10.1517/14728222.11.4.435.
van Swieten J, Spillantini MG. Hereditary frontotemporal dementia caused by Tau gene mutations. Brain Pathol. 2007, 17 (1): 63–73. PMID 17493040. doi:10.1111/j.1750-3639.2007.00052.x.
Caffrey TM, Wade-Martins R. Functional MAPT haplotypes: bridging the gap between genotype and neuropathology. Neurobiol. Dis. 2007, 27 (1): 1–10. PMC 2801069. PMID 17555970. doi:10.1016/j.nbd.2007.04.006.
Delacourte A. Tauopathies: recent insights into old diseases. Folia Neuropathol. 2005, 43 (4): 244–57. PMID 16416389.
Hirokawa N, Shiomura Y, Okabe S. Tau proteins: the molecular structure and mode of binding on microtubules. J. Cell Biol. October 1988, 107 (4): 1449–59. PMC 2115262. PMID 3139677. doi:10.1083/jcb.107.4.1449.
GeneReviews/NCBI/NIH/UW entry on MAPT-Related Disorders（页面存档备份，存于互联网档案馆）
CSF Tau positive man
一月 14, 2023
tau蛋白, 英語, proteins, 又譯濤蛋白, 是一种微管相关蛋白, 在中枢神经系统的神经元非常丰富而少见于其它细胞, 在中枢神经系统的星形胶质细胞和少突胶质细胞中表达量也很低, tau蛋白有缺陷并不再正常稳定微管时, 可导致神经系统病变和失智症, 如阿兹海默病, microtubule, associated, protein, tau微管相关蛋白tau蛋白质资料库计算机所绘制的连接在p1ni蛋白的结合区域上的mapt片段有效结构pdb, 直系同源检索, pdbe, rcsbpdb查询代码列表1i8h, . Tau蛋白 英語 Tau proteins 又譯濤蛋白 1 是一种微管相关蛋白 在中枢神经系统的神经元非常丰富而少见于其它细胞 在中枢神经系统的星形胶质细胞和少突胶质细胞中表达量也很低 2 tau蛋白有缺陷并不再正常稳定微管时 可导致神经系统病变和失智症 如阿兹海默病 Microtubule associated protein tau微管相关蛋白tau蛋白质资料库计算机所绘制的连接在P1NI蛋白的结合区域上的MAPT片段有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表1I8H 3FQP 3OVL 4E0M 4E0N 4E0O 4GLR标识代号MAPT DDPAC FTDP 17 MAPTL MSTD MTBT1 MTBT2 PPND TAU扩展标识遗传学 157140 同源基因 74962 ChEMBL 1293224 GeneCards MAPT Gene基因本体论描述分子功能 structural constituent of cytoskeleton protein binding microtubule binding SH3 domain binding enzyme binding protein kinase binding apolipoprotein binding lipoprotein particle binding细胞成分 cytosol microtubule microtubule associated complex plasma membrane axon growth cone nuclear periphery cilium axoneme tubulin complex生物过程 microtubule cytoskeleton organization neuron migration apoptotic process cellular component disassembly involved in execution phase of apoptosis axonogenesis adult walking behavior axon cargo transport regulation of autophagy regulation of microtubule polymerization positive regulation of microtubule polymerization negative regulation of intracellular transport positive regulation of axon extension mitochondrion transport along microtubule generation of neurons regulation of microtubule based movementSources Amigo QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez413717762EnsemblENSG00000186868ENSMUSG00000018411UniProtP10636P10637mRNA序列NM 001123066NM 001038609蛋白序列NP 001116538NP 001033698基因位置Chr 17 43 97 44 11 MbChr 11 104 23 104 33 MbPubMed查询 1 2 查论编tau蛋白的多种蛋白异型体是由单个基因 人类基因组中为MAPT microtubule associated protein tau 微管相关蛋白tau mRNA的選擇性剪接而形成的 3 4 1975年 它们由Marc Kirschner在普林斯顿大学的实验室中发现 5 目录 1 功能 2 结构 3 基因 4 临床意义 5 脑损伤 6 相互作用 7 另见 8 参考文献 9 进一步阅读 10 外部链接功能 编辑tau蛋白是一种高度可溶的微管相关蛋白 MAP 与非神经元细胞相较 人体内tau更多地在神经元内发现 tau蛋白的主要功能之一是维持轴突微管的稳定性 而其它神经系统中的MAPs家族蛋白也有着相似的功能 这体现在tau敲除的小鼠并没有发现其脑组织的发育受到影响 这可能是在tau缺失后 其它MAPs家族蛋白在神经元内起到代偿tau的作用 从而继续维持轴突微管的稳定 保证脑功能的正常运作 6 tau并不在树突发挥功能 而主要作用在轴突远端维持微管的稳定性和必要的灵活性 这与MAP6蛋白 位于轴突近端固定微管 与MAP2 主要维持树突的稳定性 的功能相对 Tau蛋白与微管蛋白 Tubulin 相互作用以稳定微管 同时驱动Tubulin在微管内组装 Tau蛋白通过异构和磷酸化控制微管的稳定性 结构 编辑六tau蛋白异构体存在于人类脑部组织中 以在结合区域中的编号为标识 其中三个异构体拥有三个结合区域 其余三个异构体则有四个 此结合区域位于该蛋白的羟基末端并带有正电 可与带负电的微管结合 而带有四个结合区域的异构体有更好的稳定微管的功能 此异构体则为tau基因的2 3和10号外显子被选择性剪切的产物 tau蛋白可视为一个在最长的tau蛋白异构体上拥有79个丝氨酸和苏氨酸磷酸化位点的磷酸蛋白 有报道称磷酸蛋白在普通tau蛋白的这些位点上的数量已达到30个左右 磷酸蛋白同时也受激酶宿主的控制 包括PKN 丝氨酸 苏氨酸蛋白激酶 当PKN被激活 便会磷酸化tau蛋白从而造成微管组织破坏 tau蛋白的磷酸蛋白也被先天性地控制 例如婴儿中枢神经系统的tau蛋白的磷酸化程度比成人的更高 而所有异构体中的磷酸化程度由于磷酸酶的作用会随着人年龄的增长而减弱 比如激酶 磷酸酶也在对这个tau蛋白的磷酸蛋白的调节中起到作用 基因 编辑临床意义 编辑tau蛋白 tau包含物 pTau 的过度磷酸化 英语 Hyperphosphorylation 可导致配对的螺旋丝和直丝的缠结的自组装 其参与阿茲海默症 额颞叶痴呆 和其他tau蛋白病的发病机理 7 脑损伤 编辑相互作用 编辑另见 编辑Tau蛋白病变 一类与tau蛋白积累有关的疾病 拳击员痴呆 阿兹海默病 皮质基地变性 Template 进行性核上性麻痹 蛋白质构象病 皮克氏病 17号染色体额颞叶痴呆症和帕金森氏症 朊病毒 Chronic traumatic encephalopathy CTE 慢性創傷性腦病變 参考文献 编辑 楊雨哲 孫承洲 阿茲海默症的成因及治療 30 3 2014 09 30 2015 01 23 ISSN 2220 6493 原始内容存档于2015 01 23 Shin RW Iwaki T Kitamoto T Tateishi J Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin fixed normal and Alzheimer s disease brain tissues Lab Invest May 1991 64 5 693 702 PMID 1903170 Goedert M Wischik CM Crowther RA Walker JE Klug A Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease identification as the microtubule associated protein tau Proc Natl Acad Sci U S A June 1988 85 11 4051 5 PMC 280359 PMID 3131773 doi 10 1073 pnas 85 11 4051 Goedert M Spillantini MG Jakes R Rutherford D Crowther RA Multiple isoforms of human microtubule associated protein tau sequences and localization in neurofibrillary tangles of Alzheimer s disease Neuron October 1989 3 4 519 26 PMID 2484340 doi 10 1016 0896 6273 89 90210 9 Weingarten MD Lockwood AH Hwo SY Kirschner MW A protein factor essential for microtubule assembly Proc Natl Acad Sci U S A May 1975 72 5 1858 62 PMC 432646 PMID 1057175 doi 10 1073 pnas 72 5 1858 Harada A Oguchi K Okabe S Kuno J Terada S Ohshima T Sato Yoshitake R Takei Y Noda T Hirokawa N Altered microtubule organization in small calibre axons of mice lacking tau protein Nature June 1994 369 6480 488 91 PMID 8202139 doi 10 1038 369488a0 Alonso A Zaidi T Novak M Grundke Iqbal I Iqbal K Hyperphosphorylation induces self assembly of tau into tangles of paired helical filaments straight filaments Proc Natl Acad Sci U S A June 2001 98 12 6923 8 PMC 34454 PMID 11381127 doi 10 1073 pnas 121119298 进一步阅读 编辑Goedert M Crowther RA Garner CC Molecular characterization of microtubule associated proteins tau and MAP2 Trends Neurosci 1991 14 5 193 9 PMID 1713721 doi 10 1016 0166 2236 91 90105 4 Morishima Kawashima M Hasegawa M Takio K et al Hyperphosphorylation of tau in PHF Neurobiol Aging 1995 16 3 365 71 discussion 371 80 PMID 7566346 doi 10 1016 0197 4580 95 00027 C 引文格式1维护 显式使用等标签 link Heutink P Untangling tau related dementia Hum Mol Genet 2000 9 6 979 86 PMID 10767321 doi 10 1093 hmg 9 6 979 Goedert M Spillantini MG Tau mutations in frontotemporal dementia FTDP 17 and their relevance for Alzheimer s disease Biochim Biophys Acta 2000 1502 1 110 21 PMID 10899436 doi 10 1016 S0925 4439 00 00037 5 Morishima Kawashima M Ihara Y Recent advances in Alzheimer s disease Seikagaku 2002 73 11 1297 307 PMID 11831025 Blennow K Vanmechelen E Hampel H CSF total tau Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer s disease Mol Neurobiol 2002 24 1 3 87 97 PMID 11831556 doi 10 1385 MN 24 1 3 087 Ingram EM Spillantini MG Tau gene mutations dissecting the pathogenesis of FTDP 17 Trends in molecular medicine 2003 8 12 555 62 PMID 12470988 doi 10 1016 S1471 4914 02 02440 1 Pickering Brown S The tau gene locus and frontotemporal dementia Dementia and geriatric cognitive disorders 2004 17 4 258 60 PMID 15178931 doi 10 1159 000077149 van Swieten JC Rosso SM van Herpen E et al Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17 Dementia and geriatric cognitive disorders 2004 17 4 261 4 PMID 15178932 doi 10 1159 000077150 引文格式1维护 显式使用等标签 link Kowalska A Jamrozik Z Kwiecinski H Progressive supranuclear palsy parkinsonian disorder with tau pathology Folia neuropathologica Association of Polish Neuropathologists and Medical Research Centre Polish Academy of Sciences 2004 42 2 119 23 PMID 15266787 Rademakers R Cruts M van Broeckhoven C The role of tau MAPT in frontotemporal dementia and related tauopathies Hum Mutat 2005 24 4 277 95 PMID 15365985 doi 10 1002 humu 20086 Lee HG Perry G Moreira PI et al Tau phosphorylation in Alzheimer s disease pathogen or protector Trends in molecular medicine 2005 11 4 164 9 PMID 15823754 doi 10 1016 j molmed 2005 02 008 引文格式1维护 显式使用等标签 link Hardy J Pittman A Myers A et al Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens Biochem Soc Trans 2005 33 Pt 4 582 5 PMID 16042549 doi 10 1042 BST0330582 引文格式1维护 显式使用等标签 link Deutsch SI Rosse RB Lakshman RM Dysregulation of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer s disease frontotemporal dementia and schizophrenia with therapeutic implications Prog Neuropsychopharmacol Biol Psychiatry 2007 30 8 1369 80 PMID 16793187 doi 10 1016 j pnpbp 2006 04 007 Williams DR Tauopathies classification and clinical update on neurodegenerative diseases associated with microtubule associated protein tau Internal medicine journal 2006 36 10 652 60 PMID 16958643 doi 10 1111 j 1445 5994 2006 01153 x Pittman AM Fung HC de Silva R Untangling the tau gene association with neurodegenerative disorders Hum Mol Genet 15 2006 Spec No 2 Review Issue 2 R188 95 PMID 16987883 doi 10 1093 hmg ddl190 Roder HM Hutton ML Microtubule associated protein tau as a therapeutic target in neurodegenerative disease Expert Opin Ther Targets 2007 11 4 435 42 PMID 17373874 doi 10 1517 14728222 11 4 435 van Swieten J Spillantini MG Hereditary frontotemporal dementia caused by Tau gene mutations Brain Pathol 2007 17 1 63 73 PMID 17493040 doi 10 1111 j 1750 3639 2007 00052 x Caffrey TM Wade Martins R Functional MAPT haplotypes bridging the gap between genotype and neuropathology Neurobiol Dis 2007 27 1 1 10 PMC 2801069 PMID 17555970 doi 10 1016 j nbd 2007 04 006 Delacourte A Tauopathies recent insights into old diseases Folia Neuropathol 2005 43 4 244 57 PMID 16416389 Hirokawa N Shiomura Y Okabe S Tau proteins the molecular structure and mode of binding on microtubules J Cell Biol October 1988 107 4 1449 59 PMC 2115262 PMID 3139677 doi 10 1083 jcb 107 4 1449 外部链接 编辑醫學主題詞表 MeSH tau Proteins GeneReviews NCBI NIH UW entry on MAPT Related Disorders 页面存档备份 存于互联网档案馆 MR scans of variant CJD CSF Tau positive man 取自 https zh wikipedia org w index php title Tau蛋白 amp oldid 68257447, 维基百科，wiki，书籍，书籍，图书馆，
