Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies
Open accessAbstract
Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an "unfolded" conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions.
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In neuronal tissues, accumulation of AGEs induces glycation of α-synuclein and tau proteins, leading to protein dysfunction and aggregation of harmful protein oligomers capable of initiating and developing neurodegenerative diseases.
“For instance, in neuronal tissues, the accumulation of AGEs induces glycation of α-synuclein and tau proteins, leading to protein dysfunction accompanied by the aggregation of harmful protein oligomers capable of initiating and developing neurodegenerative diseases27,28.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [27]
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Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676 · see citing works
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · see citing works
The distribution of tau in the mammalian central nervous system.
Binder, L. I., Frankfurter, A., & Rebhun, L. I. (1985) · The Journal of cell biology · doi:10.1083/jcb.101.4.1371 · Cited by 1,588 · see citing works
Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0033 · Cited by 1,364 · see citing works
Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling
Mukhopadhyay, D., & Riezman, H. (2007) · Science · doi:10.1126/science.1127085 · Cited by 1,221 · see citing works
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W. W., Huang, E. J., Shen, Y., Masliah, E., Mukherjee, C., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.044 · Cited by 949 · see citing works
Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease
Mori, H., Kondo, J., & Ihara, Y. (1987) · Science · doi:10.1126/science.3029875 · Cited by 843 · see citing works
Atypical ubiquitin chains: new molecular signals
Ikeda, F., & Đikić, I. (2008) · EMBO Reports · doi:10.1038/embor.2008.93 · Cited by 829 · see citing works
Carrell, R. W., & Lomas, D. A. (1997) · The Lancet · doi:10.1016/s0140-6736(97)02073-4 · Cited by 811 · see citing works
CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Petrucelli, L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh083 · Cited by 735 · cited 10× · see citing works
“…ubiquitylate tau, including the C-terminus of the Hsc70-interacting protein (CHIP), TNF receptor-associated factor 6 (TRAF6) and axotrophin/MARCH7 (Petrucelli et al., 2004; Babu et al., 2005; Flach et al., 2014), whereas other E3 ubiquitin ligases, such as parkin and Cbl, failed to ubiquitylate…”
BackgroundInfluentialThe acetylation of tau inhibits its function and promotes pathological tau aggregation
Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2011) · Nature Communications · doi:10.1038/ncomms1255 · Cited by 724 · see citing works
HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin.
Iwata, A., Riley, B. E., Johnston, J. A., & Kopito, R. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508786200 · Cited by 719 · see citing works
The Primary Structure and Heterogeneity of Tau Protein from Mouse Brain
Lee, G. S., Cowan, N. J., & Kirschner, M. W. (1988) · Science · doi:10.1126/science.3122323 · Cited by 680 · see citing works
Structural Polymorphism of 441-Residue Tau at Single Residue Resolution
Mukrasch, M. D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000034 · Cited by 652 · see citing works
Post-translational modifications of tau protein: Implications for Alzheimer's disease
Martin, L., Latypova, X., & Terro, F. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.023 · Cited by 645 · see citing works
Perry, G., Friedman, R., Shaw, G., & Chau, V (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.9.3033 · Cited by 623 · see citing works
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Lei, P., Ayton, S., Finkelstein, D. I., Spoerri, L., Ciccotosto, G. D., Wright, D. K., Wong, B. X. W., Adlard, P. A., Cherny, R. A., Lam, L. Q., et al. (2012) · Nature Medicine · doi:10.1038/nm.2613 · Cited by 594 · see citing works
Schweers, O., Schönbrunn, E., Marx, A., & Mandelkow�, E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51080-8 · Cited by 569 · see citing works
Neve, R. L., Harris, P. K. W., Kosik, K. S., Kurnit, D. M., & Donlon, T. A. (1986) · Molecular Brain Research · doi:10.1016/0169-328x(86)90033-1 · Cited by 565 · see citing works
Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress.
Yan, S. D., Chen, X., Schmidt, A. M., Brett, J., Godman, G., Zou, Y. S., Scott, C. W., Caputo, C., Frappier, T., & Smith, M. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7787 · Cited by 565 · see citing works
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Rissman, R. A., Poon, W. W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M. P., LaFerla, F. M., Rohn, T. T., & Cotman, C. W. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420640 · Cited by 543 · see citing works
Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits
Min, S.-W., Chen, X., Tracy, T. E., Li, Y., Zhou, Y., Wang, C., Shirakawa, K., Minami, S. S., Defensor, E., Mok, S. A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3951 · Cited by 516 · see citing works
The microtubule binding domain of tau protein
Lee, G., Neve, R. L., & Kosik, K. S. (1989) · Neuron · doi:10.1016/0896-6273(89)90050-0 · Cited by 500 · see citing works
Proteasome inhibition by paired helical filament‐tau in brains of patients with Alzheimer's disease
Keck, S., Nitsch, R., Grune, T., & Ullrich, O. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01642.x · Cited by 483 · see citing works
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
CHIP-Hsc70 Complex Ubiquitinates Phosphorylated Tau and Enhances Cell Survival
Shimura, H., Schwartz, D., Gygi, S. P., & Kosik, K. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305838200 · Cited by 469 · see citing works
Sirtuin 1 Reduction Parallels the Accumulation of Tau in Alzheimer Disease
Julien, C., Tremblay, C., Émond, V., Lebbadi, M., Salem, N., Bennett, D. A., & Calon, F. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181922348 · Cited by 467 · see citing works
Tan, J. M. M., Wong, E. S. P., Kirkpatrick, D. S., Pletniková, O., Ko, H. S., Tay, S.-P., Ho, M. W. L., Troncoso, J. C., Gygi, S. P., Lee, M. K., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm320 · Cited by 445 · see citing works
Advanced Glycation End Products in Alzheimer's Disease and Other Neurodegenerative Diseases
Sasaki, N., Fukatsu, R., Tsuzuki, K., Hayashi, Y., Yoshida, T., Fujii, N., Koike, T., WAKAYAMA, I., Yanagihara, R. T., Garruto, R. M., et al. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65659-3 · Cited by 409 · see citing works
Yan, S. D., Yan, S. F., Chen, X., Fu, J., Chen, M., Kuppusamy, P., Smith, M. A., Perry, G., Godman, G. C., Nawroth, P., et al. (1995) · Nature Medicine · doi:10.1038/nm0795-693 · Cited by 406 · see citing works
Histone deacetylase 6 interacts with the microtubule‐associated protein tau
Ding, H., Dolan, P. J., & Johnson, G. V. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05564.x · Cited by 387 · see citing works
Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau)
Dickson, D. W., Kouri, N., Murray, M. E., & Josephs, K. A. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9589-0 · Cited by 380 · see citing works
Ubch9 conjugates SUMO but not ubiquitin
Desterro, J. M. P., Thomson, J. M. D., & Hay, R. T. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01305-7 · Cited by 366 · see citing works
Preparation and Characterization of Neurotoxic Tau Oligomers
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Jackson, G. R., & Kayed, R. (2010) · Biochemistry · doi:10.1021/bi1016233 · Cited by 359 · see citing works
Spillantini, M. G., Goedert, M., Crowther, R. A., Murrell, J. R., Farlow, M. R., & Ghetti, B. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4113 · Cited by 334 · see citing works
Analysis of microtubule-associated protein tau glycation in paired helical filaments.
Ledesma, M. D., Bonay, P., Colaço, C., & Avila, J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31849-5 · Cited by 333 · cited 5× · see citing works
“…occurs preferentially at the MBD of PHF-tau (Ledesma and Avila, 1995); lysines present at the R3 repeat were initially identified to be glycated in vitro (Ledesma et al., 1994), but later studies confirmed immunologically that glycation takes place in vivo within the MBD (Ledesma and Avila, 1995).”
BackgroundInfluentialUbiquitin is conjugated with amino-terminally processed tau in paired helical filaments
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90063-w · Cited by 332 · see citing works
Proteasomal degradation of tau protein
David, D. C., Layfield, R., Serpell, L., Narain, Y., Goedert, M., & Spillantini, M. G. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01137.x · Cited by 327 · see citing works
Kovács, G. G. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020189 · Cited by 322 · see citing works
Advanced glycation end products and neurodegenerative diseases: Mechanisms and perspective
Li, J., Liu, D., Sun, L., Lu, Y., & Zhang, Z. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.02.018 · Cited by 320 · see citing works
Small Ubiquitin-like Modifier (SUMO) Modification of Natively Unfolded Proteins Tau and α-Synuclein
Dorval, V., & Fraser, P. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510127200 · Cited by 319 · see citing works
Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation
Babu, J. R., Geetha, T., & Wooten, M. W. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03181.x · Cited by 315 · see citing works
Cripps, D., Thomas, S. N., Jeng, Y., Yang, F., Davies, P., & Yang, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512786200 · Cited by 312 · see citing works
Cook, C. N., Carlomagno, Y., Gendron, T. F., Dunmore, J. H., Scheffel, K., Stetler, C. T., Davis, M., Dickson, D. W., Jarpe, M. B., Deture, M. A., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt402 · Cited by 309 · see citing works
Tau domains, phosphorylation, and interactions with microtubules
Mandelkow, E.-M., Biernat, J., Drewes, G., Gustke, N., Trinczek, B., & Mandelkow, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00025-a · Cited by 308 · see citing works
Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., Xie, S. X., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Brain · doi:10.1093/brain/aws013 · Cited by 281 · see citing works
Sinha, S., Lopes, D., Du, Z., Pang, E. S., Shanmugam, A., Lomakin, A., Talbiersky, P., Tennstaedt, A., McDaniel, K., Bakshi, R., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja206279b · Cited by 280 · see citing works
Tracy, T. E., Sohn, P. D., Minami, S. S., Wang, C., Min, S.-W., Li, Y., Zhou, Y., Le, D., Lo, I., Ponnusamy, R., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.005 · Cited by 277 · see citing works
Hernández, F., & Ávila, J. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7220-x · Cited by 263 · see citing works
Why do cellular proteins linked to K63‐polyubiquitin chains not associate with proteasomes?
Nathan, J. A., Kim, H. T., Ting, L., Gygi, S. P., & Goldberg, A. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2012.354 · Cited by 253 · see citing works
In Vitro Assembly and Recognition of Lys-63 Polyubiquitin Chains
Hofmann, R. M., & Pickart, C. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103378200 · Cited by 253 · see citing works
Dickey, C. A., Yue, M., Lin, W.-L., Dickson, D. W., Dunmore, J. H., Lee, W. C., Zehr, C., West, G., Cao, S., Clark, A. M. K., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0746-06.2006 · Cited by 248 · see citing works
Specific Knockdown of Endogenous Tau Protein by Peptide-Directed Ubiquitin-Proteasome Degradation
Chu, T.-T., Gao, N., Li, Q.-Q., Chen, P.-G., Yang, X.-F., Chen, Y.-X., Zhao, Y.-F., & Li, Y.-M. (2016) · Cell Chemical Biology · doi:10.1016/j.chembiol.2016.02.016 · Cited by 247 · see citing works
Luo, H.-B., Xia, Y.-Y., Shu, X.-J., Liu, Z.-C., Feng, Y., Liu, X.-H., Yu, G., Yin, G., Xiong, Y.-S., Zeng, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417548111 · Cited by 236 · see citing works
Williamson, R., Scales, T., Clark, B. R., Gibb, G., Reynolds, C. H., Kellie, S., Bird, I. N., Varndell, I. M., Sheppard, P. W., Everall, I., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00010.2002 · Cited by 227 · see citing works
Akt and CHIP coregulate tau degradation through coordinated interactions
Dickey, C. A., Koren, J., Zhang, Y.-J., Xu, Y.-F., Jinwal, U. K., Birnbaum, M. J., Monks, B., Sun, M., Cheng, J. Q., Patterson, C., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709180105 · Cited by 226 · see citing works
Identification of nuclear tau isoforms in human neuroblastoma cells.
Loomis, P. A., Howard, T. H., Castleberry, R. P., & Binder, L. I. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8422 · Cited by 217 · see citing works
Ferrer, I., López-González, I., Carmona, M., Arregui, L., Dalfó, E., Torrejón-Escribano, B., Diehl, R., & Kovacs, G. G. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000030 · Cited by 217 · see citing works
Nonenzymatic glucosylation and glucose-dependent cross-linking of protein.
Eble, A. S., Thorpe, S. R., & Baynes, J. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44682-5 · Cited by 214 · see citing works
In vivo evidence of CHIP up‐regulation attenuating tau aggregation
Sahara, N., Murayama, M., Mizoroki, T., Urushitani, M., Imai, Y., Takahashi, R., Murata, S., Tanaka, K., & Takashima, A. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03272.x · Cited by 208 · see citing works
AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation
Li, X., Lv, B.-L., Xie, J., Liu, J., Zhou, X., & Wang, J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.003 · Cited by 207 · see citing works
Lüth, H. J. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh123 · Cited by 186 · see citing works
Bancher, C., Grundke, I., Iqbal, K., Fried, V. A., Smith, H. T., & Wisniewski, H. M. (1991) · Brain Research · doi:10.1016/0006-8993(91)90681-k · Cited by 185 · see citing works
Gong, L., Li, B., Millas, S. G., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00367-1 · Cited by 180 · see citing works
Sohn, P. D., Tracy, T. E., Son, H.-I., Zhou, Y., Leite, R. E. P., Miller, B. L., Seeley, W. W., Grinberg, L. T., & Gan, L. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0109-0 · Cited by 160 · see citing works
Glia in the pathogenesis of neurodegenerative diseases
Verkhratsky, A., Parpura, V., Pekna, M., Pekny, M., & Sofroniew, M. V. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140107 · Cited by 157 · see citing works
The microtubule-associated tau protein has intrinsic acetyltransferase activity
Cohen, T. J., Friedmann, D., Hwang, A. W., Marmorstein, R., & Lee, V. M. Y. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2555 · Cited by 149 · see citing works
A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway
Dolan, P. J., & Johnson, G. V. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.110940 · Cited by 147 · see citing works
Sumoylation and human disease pathogenesis
Sarge, K. D., & Park-Sarge, O.-K. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.01.004 · Cited by 144 · see citing works
Funk, K. E., Thomas, S. N., Schafer, K. N., Cooper, G. L., Liao, Z., Clark, D. J., Yang, A. J., & Kuret, J. (2014) · Biochemical Journal · doi:10.1042/bj20140372 · Cited by 142 · see citing works
Necula, M., & Kuret, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405527200 · Cited by 136 · see citing works
Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation
Cook, C. N., Gendron, T. F., Scheffel, K., Carlomagno, Y., Dunmore, J. H., Deture, M. A., & Petrucelli, L. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds125 · Cited by 129 · see citing works
Acetylated Tau Neuropathology in Sporadic and Hereditary Tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., McCarty-Wood, E., Van Deerlin, V. M., Lee, V. M.-Y., & Trojanowski, J. Q. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.04.025 · Cited by 125 · see citing works
Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes
Xu, Z., Kohli, E., Devlin, K. I., Bold, M. S., Nix, J. C., & Misra, S. (2008) · BMC Structural Biology · doi:10.1186/1472-6807-8-26 · Cited by 124 · see citing works
Thomas, S. N., Funk, K. E., Wan, Y., Liao, Z., Davies, P., Kuret, J., & Yang, A. J. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0893-0 · Cited by 123 · see citing works
Nakashima, H., Ishihara, T., Suguimoto, S. P., Yokota, O., Oshima, E., Kugo, A., Terada, S., Hamamura, T., Trojanowski, J. Q., Lee, V. M. ‐., et al. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1087-4 · Cited by 119 · see citing works
Kuhla, B., Haase, C., Flach, K., Lüth, H.-J., Arendt, T., & Münch, G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609521200 · Cited by 119 · see citing works
Wang, P., Joberty, G., Buist, A., Vanoosthuyse, A., Stancu, I., Vasconcelos, B., Pierrot, N., Faelth-Savitski, M., Kienlen‐Campard, P., Octave, J., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1663-9 · Cited by 118 · see citing works
Choi, B.-R., Cho, W.-H., Kim, J., Lee, H. J., Chung, C., Jeon, W. K., & Han, J.-S. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.147 · Cited by 111 · see citing works
Light and electron microscope localization of the microtubule- associated tau protein in rat brain
Migheli, A., Butler, M., Brown, K., & Shelanski, M. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-06-01846.1988 · Cited by 109 · see citing works
τ Protein from Alzheimer's Disease Patients Is Glycated at Its Tubulin‐Binding Domain
Ledesma, M. D., Bonay, P., & Avila, J. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65041658.x · Cited by 109 · see citing works
Weeraratna, A. T., Kalehua, A. N., DeLeon, I., Bertak, D., Maher, G., Wade, M. S., Lustig, A., Becker, K. G., Wood, W. W., Walker, D. G., et al. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.10.028 · Cited by 109 · see citing works
Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies
Yoshida, M. (2006) · Neuropathology · doi:10.1111/j.1440-1789.2006.00743.x · Cited by 108 · see citing works
Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation
Grinberg, L. T., Wang, X., Wang, C., Sohn, P., Theofilas, P., Sidhu, M., Arevalo, J. B., Heinsen, H., Huang, E. J., Rosen, H. J., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1080-2 · Cited by 107 · see citing works
Luo, Y., Ma, B., Nussinov, R., & Wei, G. (2014) · The Journal of Physical Chemistry Letters · doi:10.1021/jz501457f · Cited by 107 · see citing works
Pallas‐Bazarra, N., Jurado‐Arjona, J., Navarrete, M., Esteban, J. A., Hernández, F., Ávila, J., & Llorens‐Martín, M. (2016) · The EMBO Journal · doi:10.15252/embj.201593518 · Cited by 101 · see citing works
Acetylation mimic of lysine 280 exacerbates human Tau neurotoxicity in vivo
Gorsky, M. K., Burnouf, S., Dols, J., Mandelkow�, E., & Partridge, L. (2016) · Scientific Reports · doi:10.1038/srep22685 · Cited by 93 · see citing works
Grune, T., Botzen, D., Engels, M., Voß, P., Kaiser, B., Jung, T., Grimm, S., Ermak, G., & Davies, K. J. A. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.008 · Cited by 85 · see citing works
Is Huntington's disease a tauopathy?
Gratuze, M., Cisbani, G., Cicchetti, F., & Planel, E. (2016) · Brain · doi:10.1093/brain/aww021 · Cited by 81 · see citing works
Takahashi, K., Ishida, M., Komano, H., & Takahashi, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.012 · Cited by 75 · see citing works
Autoacetylation Regulates P/CAF Nuclear Localization
Blanco-García, N., Asensio-Juan, E., de la Cruz, X., & Martínez‐Balbás, M. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806075200 · Cited by 73 · see citing works
Nuclear Magnetic Resonance Analysis of the Acetylation Pattern of the Neuronal Tau Protein
Kamah, A., Huvent, I., Cantrelle, F., Qi, H., Lippens, G. M., Landrieu, I., & Smet‐Nocca, C. (2014) · Biochemistry · doi:10.1021/bi500006v · Cited by 73 · see citing works
Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity
Lee, J. H., Shin, S. K., Jiang, Y., Choi, W. H., Hong, C., Kim, D., & Lee, M. J. (2015) · Scientific Reports · doi:10.1038/srep10757 · Cited by 69 · see citing works
An immunochemical study on tau glycation in paired helical filaments
Ko, L., Ko, E. C., Nacharaju, P., Liu, W.-K., Chang, E. C., Kenessey, Á., & Yen, S.-H. C. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01415-8 · Cited by 67 · see citing works
SUMO1 Affects Synaptic Function, Spine Density and Memory
Matsuzaki, S., Lee, L., Knock, E., Srikumar, T., Sakurai, M., Hazrati, L., Katayama, T., Staniszewski, A., Raught, B., Arancio, O., et al. (2015) · Scientific Reports · doi:10.1038/srep10730 · Cited by 66 · see citing works
Regulation of p53 function by lysine methylation
West, L. E., & Gozani, O. (2011) · Epigenomics · doi:10.2217/epi.11.21 · Cited by 65 · see citing works
Ubiquitination and cysteine nitrosylation during aging and Alzheimer's disease
Riederer, I. M., Schiffrin, M., Kövari, E., Bouras, C., & Riederer, B. M. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.04.018 · Cited by 60 · see citing works
Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property
Liu, K., Liu, Y., Li, L., Qin, P., Iqbal, J., Deng, Y., & Qing, H. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.002 · Cited by 60 · see citing works
Nisticò, R., Ferraina, C., Marconi, V., Blandini, F., Negri, L., Egebjerg, J., & Feligioni, M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00063 · Cited by 59 · see citing works
Flach, K., Ramminger, E., Hilbrich, I., Arsalan-Werner, A., Albrecht, F., Herrmann, L., Goedert, M., Arendt, T., & Holzer, M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.029 · Cited by 58 · see citing works
Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation
Cohen, T. J., Constance, B. H., Hwang, A. W., James, M., & Yuan, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158470 · Cited by 56 · see citing works
Characterization of In Vitro Glycation Sites of Tau
Nacharaju, P., Ko, L., & Yen, S.-H. C. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69041709.x · Cited by 43 · see citing works
Iwatsubo, T., Hasegawa, M., Esaki, Y., & Ihara, Y. (1992) · PubMed Central · Cited by 42 · see citing works
SUMO-1 is Associated with a Subset of Lysosomes in Glial Protein Aggregate Diseases
Wong, M. B., Goodwin, J., Norazit, A., Meedeniya, A. C. B., Richter‐Landsberg, C., Gai, W., & Pountney, D. L. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9358-z · Cited by 42 · see citing works
The in vitro formation of recombinant τ polymers
Ledesma, M. D., Medina, M., & Ávila, J. (1996) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815107 · Cited by 35 · see citing works
García‐Sierra, F., Jarero-Basulto, J. J., Krištofíková, Z., Majer, E., Binder, L. I., & Řı́pová, D. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00525.x · Cited by 34 · see citing works
Zhang, Y.-J., Xu, Y., Liu, X., Li, D., Yin, J., Liu, Y.-H., Chen, X., & Wang, J. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-007-0857-7 · Cited by 20 · see citing works
Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members
Hwang, A. W., Trzeciakiewicz, H., Friedmann, D., Yuan, C., Marmorstein, R., Lee, V. M. ‐., & Cohen, T. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168913 · Cited by 18 · see citing works
Plasma SUMO1 Protein is Elevated in Alzheimer’s Disease
Cho, S.-J., Yun, S., Lee, D.-H., Jo, C., Park, M. H., Han, C., & Koh, Y. H. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150103 · Cited by 17 · see citing works
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Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women
Yan, Y., Wang, X., Chaput, D., Shin, M.-K., Koh, Y., Gan, L., Pieper, A. A., Woo, J.-A. A., & Kang, D. E. (2022) · Cell · doi:10.1016/j.cell.2022.09.002 · Cited by 144 · see citing works
Brotzakis, Z. F., Lindstedt, P. R., Taylor, R. J., Rinauro, D. J., Gallagher, N. C. T., Bernardes, G. J. L., & Vendruscolo, M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00585 · Cited by 70 · see citing works
Puangmalai, N., Sengupta, U., Bhatt, N., Gaikwad, S., Montalbano, M., Bhuyan, A., Garcia, S., McAllen, S., Sonawane, M., Jerez, C., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101766 · Cited by 68 · see citing works
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
“However, there are methyltransferases of the same class, such as G9a and SUV39, which shuttle between the nucleus and cytoplasm to act on cytoplasmic proteins [87,88].”
BackgroundQuantification of Tau Protein Lysine Methylation in Aging and Alzheimer’s Disease
Huseby, C. J., Hoffman, C. N., Cooper, G. L., Cocuron, J.-C., Alonso, A. P., Thomas, S. N., Yang, A. J., & Kuret, J. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190604 · Cited by 54 · see citing works
Mullane, K., & Williams, M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.027 · Cited by 32 · see citing works
- Authors
- Kontaxi, C., Piccardo, P., & Gill, A. C.
- Affiliations
- Roslin Institute (GB)
- Corresponding author
- Gill, Andrew C.
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2017-08-11
- Volume
- 4
- Pages
- 56-56
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC5554484
- OpenAlex
- W2744353305
- Cited by
- 138
- References
- 109
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 15 · 2023: 17 · 2022: 19 · 2021: 24 · 2020: 17 · 2019: 9 · 2018: 19
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/J004332/1, BB/P013759/1)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- tau protein, lysine post-translational modifications, Alzheimer's disease, tauopathy, tau hyperphosphorylation, lysine acetylation, lysine methylation, ubiquitination, SUMOylation, glycation, tau conformation, microtubule stabilization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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