Lysine 63-linked ubiquitination of tau oligomers contributes to the pathogenesis of Alzheimer’s disease
Open accessAbstract
Ubiquitin-modified tau aggregates are abundantly found in human brains diagnosed with Alzheimer's disease (AD) and other tauopathies. Soluble tau oligomers (TauO) are the most neurotoxic tau species that propagate pathology and elicit cognitive deficits, but whether ubiquitination contributes to tau formation and spreading is not fully understood. Here, we observed that K63-linked, but not K48-linked, ubiquitinated TauO accumulated at higher levels in AD brains compared with age-matched controls. Using mass spectrometry analyses, we identified 11 ubiquitinated sites on AD brain-derived TauO (AD TauO). We found that K63-linked TauO are associated with enhanced seeding activity and propagation in human tau-expressing primary neuronal and tau biosensor cells. Additionally, exposure of tau-inducible HEK cells to AD TauO with different ubiquitin linkages (wild type, K48, and K63) resulted in enhanced formation and secretion of K63-linked TauO, which was associated with impaired proteasome and lysosome functions. Multipathway analysis also revealed the involvement of K63-linked TauO in cell survival pathways, which are impaired in AD. Collectively, our study highlights the significance of selective TauO ubiquitination, which could influence tau aggregation, accumulation, and subsequent pathological propagation. The insights gained from this study hold great promise for targeted therapeutic intervention in AD and related tauopathies.
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K63-linked accumulation of ubiquitinated tau is associated with tau seeding.
“In human AD brains, K63-linked accumulation of ubiquitinated tau is associated with tau seeding (41).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [41]
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Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
2021 Alzheimer's disease facts and figures
Anonymous (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12328 · Cited by 2,236 · see citing works
Swatek, K. N., & Komander, D. (2016) · Cell Research · doi:10.1038/cr.2016.39 · Cited by 2,070 · see citing works
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · 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
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
CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Petrucelli, L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh083 · Cited by 735 · see citing works
The 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
Proteopathic tau seeding predicts tauopathy in vivo
Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696 · see citing works
The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update
Siddiqui, W. A., Ahad, A., & Ahsan, H. (2015) · Archives of Toxicology · doi:10.1007/s00204-014-1448-7 · Cited by 689 · see citing works
The release and trans-synaptic transmission of Tau via exosomes
Wang, Y., Balaji, V., Kaniyappan, S., Krüger, L., Irsen, S., Tepper, K., Chandupatla, R., Maetzler, W., Schneider, A., Mandelkow, E., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0143-y · Cited by 674 · see citing works
A First Line of Stress Defense: Small Heat Shock Proteins and Their Function in Protein Homeostasis
Haslbeck, M., & Vierling, E. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.02.002 · Cited by 633 · see citing works
Propagation of Tau aggregates and neurodegeneration
Goedert, M., Eisenberg, D. S., & Crowther, R. A. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031153 · Cited by 632 · see citing works
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Novel tau filament fold in corticobasal degeneration
Zhang, W., Tarutani, A., Newell, K. L., Murzin, A. G., Matsubara, T., Falcon, B., Vidal, R., Garringer, H. J., Shi, Y., Ikeuchi, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2043-0 · Cited by 546 · see citing works
Identification of oligomers at early stages of tau aggregation in Alzheimer's disease
Lasagna‐Reeves, C. A., Castillo‐Carranza, D. L., Sengupta, U., Sarmiento, J., Troncoso, J., Jackson, G. R., & Kayed, R. (2012) · The FASEB Journal · doi:10.1096/fj.11-199851 · Cited by 527 · see citing works
Self-citationAccumulation of Pathological Tau Species and Memory Loss in a Conditional Model of Tauopathy
Berger, Z., Roder, H. M., Hanna, A., Carlson, A. M., Rangachari, V., Yue, M., Wszołek, Z. K., Ashe, K. H., Knight, J. A., Dickson, D. W., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0587-07.2007 · Cited by 485 · see citing works
Seyfried, N. T., Dammer, E. B., Swarup, V., Nandakumar, D., Duong, D. M., Yin, L., Deng, Q., Nguyen, T., Hales, C. M., Wingo, T., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2016.11.006 · Cited by 477 · see citing works
A current view on Tau protein phosphorylation in Alzheimer's disease
Wegmann, S., Biernat, J., & Mandelkow�, E. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.03.003 · Cited by 464 · see citing works
Myeku, N., Clelland, C. L., Emrani, S., Kukushkin, N. V., Yu, W. H., Goldberg, A. L., & Duff, K. E. (2016) · Nature Medicine · doi:10.1038/nm.4011 · Cited by 446 · 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 444 · see citing works
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Tau association with synaptic vesicles causes presynaptic dysfunction
Zhou, L., McInnes, J., Wierda, K., Holt, M., Herrmann, A. G., Jackson, R. J., Wang, Y.-C., Swerts, J., Beyens, J., Miskiewicz, K., et al. (2017) · Nature Communications · doi:10.1038/ncomms15295 · Cited by 434 · see citing works
Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 415 · see citing works
Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains
Arakhamia, T., Lee, C. E., Carlomagno, Y., Kumar, M., Duong, D. M., Wesseling, H., Kundinger, S. R., Wang, K., Williams, D., Deture, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.027 · Cited by 400 · see citing works
Neurons May Live for Decades with Neurofibrillary Tangles
Morsch, R., Simon, W., & Coleman, P. D. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199902000-00008 · Cited by 370 · see citing works
Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
Tau degradation: The ubiquitin–proteasome system versus the autophagy-lysosome system
Lee, M. J., Lee, J. H., & Rubinsztein, D. C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.001 · Cited by 364 · 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
Self-citationA common mechanism of proteasome impairment by neurodegenerative disease-associated oligomers
Thibaudeau, T. A., Anderson, R. T., & Smith, D. M. (2018) · Nature Communications · doi:10.1038/s41467-018-03509-0 · Cited by 356 · see citing works
Ubiquitin 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
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
Endoplasmic reticulum stress and inflammation in the central nervous system
Sprenkle, N. T., Sims, S. G., Sánchez, C. L., & Meares, G. P. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0183-y · Cited by 299 · see citing works
Chen, X., & Mobley, W. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00659 · Cited by 291 · see citing works
Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · cited 1× · see citing works
“Soluble tau oligomers have been identified as the more toxic species and most relevant to disease progression (8, 13).”
BackgroundSelf-citationTemplate-assisted filament growth by parallel stacking of tau
Margittai, M., & Langen, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401911101 · Cited by 276 · see citing works
Abisambra, J. F., Jinwal, U. K., Blair, L. J., O’Leary, J. C., Li, Q., Brady, S., Wang, L., Guidi, C., Zhang, B., Nordhues, B. A., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5397-12.2013 · Cited by 268 · 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
Usenovic, M., Niroomand, S., Drolet, R. E., Yao, L., Gaspar, R. C., Hatcher, N. G., Schachter, J., Renger, J. J., & Parmentier-Batteur, S. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1523-15.2015 · Cited by 245 · see citing works
Kumar, V., Kundu, S., Singh, A., & Singh, S. (2022) · Current Neuropharmacology · doi:10.2174/1570159x19666210609160017 · Cited by 210 · see citing works
Taniguchi-Watanabe, S., Arai, T., Kametani, F., Nonaka, T., Masuda-Suzukake, M., Tarutani, A., Murayama, S., Saito, Y., Arima, K., Yoshida, M., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1503-3 · Cited by 200 · see citing works
Intracellular Trafficking of Histone Deacetylase 4 Regulates Neuronal Cell Death
Bolger, T. A., & Yao, T. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1826-05.2005 · Cited by 190 · see citing works
Epidermal growth factor receptor is a preferred target for treating Amyloid-β–induced memory loss
Wang, L., Chiang, H.-C., Wu, W., Liang, B., Xie, Z., Yao, X., Ma, W., Du, S., & Zhong, Y. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208011109 · Cited by 190 · see citing works
The Ubiquitin-Proteasome System and the Autophagic-Lysosomal System in Alzheimer Disease
Ihara, Y., Morishima-Kawashima, M., & Nixon, R. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006361 · Cited by 190 · see citing works
Acetylation Disfavors Tau Phase Separation
Ferreon, J. C., Jain, A., Choi, K.-J., Tsoi, P. S., MacKenzie, K. R., Jung, S. Y., & Ferreon, A. C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051360 · Cited by 183 · see citing works
Regional protein expression in human Alzheimer’s brain correlates with disease severity
Xu, J., Patassini, S., Rustogi, N., Riba‐Garcia, I., Hale, B. D., Phillips, A. M., Waldvogel, H. J., Haines, R., Bradbury, P., Stevens, A., et al. (2019) · Communications Biology · doi:10.1038/s42003-018-0254-9 · Cited by 182 · see citing works
Castillo‐Carranza, D. L., Gerson, J. E., Sengupta, U., Guerrero‐Munoz, M. J., Lasagna‐Reeves, C. A., & Kayed, R. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132477 · Cited by 180 · see citing works
Self-citationCSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease
Horie, K., Barthélemy, N. R., Sato, C., & Bateman, R. J. (2021) · Brain · doi:10.1093/brain/awaa373 · Cited by 180 · see citing works
Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody
Albert, M., Mairet‐Coello, G., Danis, C., Lieger, S., Caillierez, R., Carrier, S., Skrobala, E., Landrieu, I., Michel, A., Schmitt, M., et al. (2019) · Brain · doi:10.1093/brain/awz100 · Cited by 177 · see citing works
Nilson, A. N., English, K. C., Gerson, J. E., Whittle, T. B., Crain, C. N., Xue, J. J., Sengupta, U., Castillo‐Carranza, D. L., Zhang, W., Gupta, P. K., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160912 · Cited by 170 · see citing works
Self-citationTargeting Autophagy for the Treatment of Alzheimer’s Disease: Challenges and Opportunities
Liu, J., & Li, L. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00203 · Cited by 159 · see citing works
Silva, M. C., Nandi, G. A., Tentarelli, S., Gurrell, I. K., Jamier, T., Lucente, D., Dickerson, B. C., Brown, D. G., Brandon, N. J., & Haggarty, S. J. (2020) · Nature Communications · doi:10.1038/s41467-020-16984-1 · Cited by 157 · see citing works
Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease
Galasko, D. R., Clark, C., Chang, L., Miller, B. L., Green, R. C., Motter, R. N., & Seubert, P. A. (1997) · Neurology · doi:10.1212/wnl.48.3.632 · Cited by 153 · see citing works
Koss, D. J., Jones, G., Cranston, A., Gardner, H., Kanaan, N. M., & Platt, B. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1632-3 · Cited by 149 · see citing works
Blom, E. S., Giedraitis, V., Zetterberg, H., Fukumoto, H., Blennow, K., Hyman, B. T., Irizarry, M. C., Wahlund, L., Lannfelt, L., & Ingelsson, M. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000216841 · Cited by 141 · see citing works
Kontaxi, C., Piccardo, P., & Gill, A. C. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00056 · Cited by 138 · see citing works
Amyloid-β Annular Protofibrils Evade Fibrillar Fate in Alzheimer Disease Brain
Lasagna‐Reeves, C. A., Glabe, C. G., & Kayed, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.236257 · Cited by 136 · see citing works
Self-citationRoberts, M., Sevastou, I., Imaizumi, Y., Mistry, K., Talma, S., Dey, M., Gartlon, J., Ochiai, H., Zhou, Z., Akasofu, S., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-0884-2 · Cited by 135 · see citing works
A Role for Calcineurin in Alzheimers Disease
Reese, L. C., & Taglialatela, G. (2011) · Current Neuropharmacology · doi:10.2174/157015911798376316 · Cited by 131 · see citing works
P53 aggregation, interactions with tau, and impaired DNA damage response in Alzheimer’s disease
Farmer, K. M., Ghag, G., Puangmalai, N., Montalbano, M., Bhatt, N. N., & Kayed, R. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01012-6 · Cited by 126 · see citing works
Self-citationBrunden, K. R., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14406 · Cited by 125 · see citing works
Brain site-specific proteome changes in aging-related dementia
Manavalan, A., Mishra, M., Feng, L., Sze, S. K., Akatsu, H., & Heese, K. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.76 · Cited by 114 · see citing works
Chen, X., Li, Y., Wang, C., Tang, Y., Mok, S., Tsai, R. M., Rojas, J. C., Karydas, A., Miller, B. L., Boxer, A. L., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0354-0 · Cited by 113 · see citing works
Mielcarek, M., Zielonka, D., Carnemolla, A., Marcinkowski, T., & Guidez, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00042 · Cited by 111 · see citing works
A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy
Trzeciakiewicz, H., Tseng, J., Wander, C. M., Madden, V. J., Tripathy, A., Yuan, C., & Cohen, T. J. (2017) · Scientific Reports · doi:10.1038/srep44102 · Cited by 110 · see citing works
Puangmalai, N., Bhatt, N. N., Montalbano, M., Sengupta, U., Gaikwad, S., Ventura, F. L., McAllen, S., Ellsworth, A., García, S., & Kayed, R. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2503-3 · Cited by 110 · see citing works
Self-citationMechanically induced development and maturation of human intestinal organoids in vivo
Poling, H. M., Wu, D. X.-Y., Brown, N. E., Baker, M. L., Hausfeld, T. A., Huynh, N., Chaffron, S., Dunn, J., Hogan, S. P., Wells, J. M., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0243-9 · Cited by 107 · see citing works
Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity
Kudo, W., Hp, L., Smith, M. A., Zhu, X., Matsuyama, S., & Lee, H.-G. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.43 · Cited by 104 · see citing works
Pathological Changes of Tau Related to Alzheimer’s Disease
Chu, D., & Liu, F. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00457 · Cited by 103 · see citing works
Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease
Abreha, M. H., Dammer, E. B., Ping, L., Zhang, T., Duong, D. M., Gearing, M., Lah, J. J., Levey, A. I., & Seyfried, N. T. (2018) · PROTEOMICS · doi:10.1002/pmic.201800108 · Cited by 81 · see citing works
de Calignon, A., Spires-Jones, T. L., Pitstick, R., Carlson, G. A., & Hyman, B. T. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9fc66 · Cited by 81 · see citing works
Tau oligomers in cerebrospinal fluid in Alzheimer's disease
Sengupta, U., Portelius, E., Hansson, O., Farmer, K., Castillo‐Carranza, D., Woltjer, R., Zetterberg, H., Galasko, D., Blennow, K., & Kayed, R. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.382 · Cited by 77 · see citing works
Self-citationThe Ubiquitin System in Alzheimer’s Disease
Harris, L. D., Jasem, S., & Licchesi, J. D. F. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-38266-7_8 · Cited by 76 · see citing works
Ubiquitin Signaling and Degradation of Aggregate-Prone Proteins
Galves, M., Rathi, R., Prag, G., & Ashkenazi, A. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.04.007 · Cited by 73 · see citing works
Neurofibrillary Tangles May Interfere With Smad 2/3 Signaling in Neurons
Chalmers, K. A., & Love, S. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3180303b93 · Cited by 66 · see citing works
Zhao, Y., & Brasier, A. R. (2013) · Methods · doi:10.1016/j.ymeth.2013.02.001 · Cited by 56 · see citing works
Self-citationHDAC4 protects cells from ER stress induced apoptosis through interaction with ATF4
Zhang, P., Sun, Q., Zhao, C., Ling, S., Li, Q., Chang, Y.-Z., & Li, Y. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2013.11.026 · Cited by 54 · see citing works
Wu, Y., Hou, F., Wang, X., Kong, Q., Han, X., & Bai, B. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00114 · Cited by 52 · see citing works
Zheng, J., Akbari, M., Schirmer, C., Reynaert, M., Loyens, A., Lefebvre, B., Buée, L., Croteau, D. L., Galas, M., & Bohr, V. A. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00896-8 · Cited by 51 · see citing works
Modulating disease-relevant tau oligomeric strains by small molecules
Cascio, F. L., García, S., Montalbano, M., Puangmalai, N., McAllen, S., Pace, A., Piccionello, A. P., & Kayed, R. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.014630 · Cited by 51 · see citing works
Self-citationKnockin’ on heaven’s door: Molecular mechanisms of neuronal tau uptake
La‐Rocque, S. D., Moretto, E., Butnaru, I., & Schiavo, G. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15144 · Cited by 42 · see citing works
Immunoreactivity to Lys63-linked polyubiquitin is a feature of neurodegeneration
Paine, S., Bedford, L., Thorpe, J. R., Mayer, R. J., Cavey, J. R., Bajaj, N., Sheppard, P. W., Lowe, J., & Layfield, R. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.05.074 · Cited by 41 · see citing works
Wu, X., Shen, Q., Zhang, Z., Zhang, D., Gu, Y., & Xing, D. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02399-2 · Cited by 40 · see citing works
Abskharon, R. N. N., Seidler, P. M., Sawaya, M. R., Cascio, D., Yang, T. P., Philipp, S., Williams, C. K., Newell, K. L., Ghetti, B. F., Deture, M. A., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013638 · Cited by 31 · see citing works
Tau hyperphosphorylation affects Smad 2/3 translocation
Baig, S., Helmond, Z. V., & Love, S. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.06.045 · Cited by 30 · see citing works
Cellular Models for the Study of PrionsPreprint
Holmes, B. B., & Diamond, M. I. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024026 · Cited by 22 · see citing works
Chen, X., Wang, C., Zhou, S., Li, X., & Wu, L. (2018) · Medical Science Monitor · doi:10.12659/msm.907809 · Cited by 21 · see citing works
Severe oligomeric tau toxicity can be reversed without long-term sequelae
Martinisi, A., Flach, M., Sprenger, F., Frank, S., Tolnay, M., & Winkler, D. T. (2020) · Brain · doi:10.1093/brain/awaa445 · Cited by 20 · see citing works
Proteasome Assay in Cell Lysates
Maher, P. A. (2014) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1028 · Cited by 15 · see citing works
Yadikar, H., Johnson, C., Pafundi, N., Mouhawasse, E., Nguyen, L. T., Torres, I., Kurup, M., Yang, Z., Kobeissy, F. H., Yost, R. A., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205213 · Cited by 12 · see citing works
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Cellular and pathological functions of tau
Bravo, C. P., Naguib, S. A., & Gan, L. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00753-9 · Cited by 245 · see citing works
Hamzé, R., Delangre, E., Tolu, S., Moreau, M., Janel, N., Bailbé, D., & Movassat, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315287 · Cited by 163 · 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
Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
Sun, Z., Kwon, J.-S., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A. J., et al. (2024) · Science · doi:10.1126/science.adl2992 · Cited by 77 · see citing works
“In human AD brains, K63-linked accumulation of ubiquitinated tau is associated with tau seeding (41).”
Targeting tau in Alzheimer's disease: from mechanisms to clinical therapy
Ye, J., Wan, H., Chen, S., & Liu, G. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385847 · Cited by 69 · see citing works
Protein aggregation and its affecting mechanisms in neurodegenerative diseases
Wu, J., Wu, J., Chen, T., Cai, J., & Ren, R. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105880 · Cited by 61 · see citing works
Gaikwad, S., Puangmalai, N., Sonawane, M., Montalbano, M., Price, R., Iyer, M. S., Ray, A., Moreno, S., & Kayed, R. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adj5958 · Cited by 46 · see citing works
Self-citationTau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities
Wang, L., Banesh, S., Kumar, R., Schedin‐Weiss, S., Tjernberg, L. O., & Winblad, B. G. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70048 · Cited by 45 · see citing works
Bodily, T. A., Ramanathan, A., Wei, S., Karkisaval, A. G., Bhatt, N. N., Jerez, C., Haque, M. A., Ramil, A., Heda, P., Wang, Y., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311565120 · Cited by 37 · see citing works
Self-citationPhosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP
Nadel, C. M., Pokhrel, S., Wucherer, K., Oehler, A., Thwin, A. C., Basu, K., Callahan, M. D., Southworth, D. R., Mordes, D. A., Craik, C. S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52075-1 · Cited by 36 · see citing works
Hu, J., Sha, W., Yuan, S., Wu, J., & Huang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241915023 · Cited by 35 · see citing works
Cascio, F. L., Park, S., Sengupta, U., Puangmalai, N., Bhatt, N. N., Shchankin, N., Jerez, C., Moreno, N., Bittar, A., Xavier, R., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-07499-w · Cited by 35 · see citing works
Self-citationThe autophagy adaptor TRIAD3A promotes tau fibrillation by nested phase separation
Zhou, J., Chuang, Y. ‘., Redding‐Ochoa, J., Zhang, R., Platero, A. J., Barrett, A., Troncoso, J. C., Worley, P. F., & Zhang, W. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01461-4 · Cited by 33 · see citing works
Yang, J., Shen, N., Shen, J., Yang, Y., & Li, H.-L. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03867-x · Cited by 32 · see citing works
Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology
Kalyaanamoorthy, S., Opare, S. K. A., Xu, X., Ganesan, A., & Rao, P. P. N. (2024) · Current Alzheimer Research · doi:10.2174/0115672050301407240408033046 · Cited by 31 · see citing works
Bhopatkar, A. A., & Kayed, R. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105122 · Cited by 27 · see citing works
Self-citationAmyloid-β oligomers increase the binding and internalization of tau oligomers in human synapses
Kadamangudi, S., Marcatti, M., Zhang, W.-R., Fracassi, A., Kayed, R., Limon, A., & Taglialatela, G. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02839-2 · Cited by 25 · see citing works
Self-citationTangavelou, K., & Bhaskar, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212335 · Cited by 24 · see citing works
Dhakal, S., Robang, A. S., Bhatt, N. N., Puangmalai, N., Fung, L., Kayed, R., Paravastu, A. K., & Rangachari, V. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102498 · Cited by 23 · see citing works
Self-citationKotarba, S., Kozłowska, M., Scios, M., Saramowicz, K., Barczuk, J., Granek, Z., Siwecka, N., Wiese, W., Golberg, M., Galita, G., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910797 · Cited by 21 · see citing works
Alzheimer proteopathic tau seeds are biochemically a forme fruste of mature paired helical filaments
Kumar, M., Quittot, N., Dujardin, S., Schlaffner, C. N., Viodé, A., Wiedmer, A. E., Beerepoot, P., Chun, J. E., Glynn, C. A., Fernandes, A. R., et al. (2024) · Brain · doi:10.1093/brain/awad378 · Cited by 20 · see citing works
Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta
Zhang, C., Jia, Q., Zhu, L., Hou, J., Wang, X., Li, D., Zhang, J., Zhang, Y., Su, Y., Tu, Z., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14122 · Cited by 19 · see citing works
Bittar, A., Al-Lahham, R., Bhatt, N., Moore, K., Montalbano, M., Jerez, C., Fung, L., McAllen, S., Ellsworth, A., & Kayed, R. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220518 · Cited by 18 · see citing works
Self-citationSato, Y., Terawaki, S., Oikawa, D., Shimizu, K., Okina, Y., Ito, H., & Tokunaga, F. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1089213 · Cited by 17 · see citing works
Puangmalai, N., Bhatt, N. N., Bittar, A., Jerez, C., Shchankin, N., & Kayed, R. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102562 · Cited by 17 · see citing works
Self-citationMolecular mechanisms implicated in protein changes in the Alzheimer’s disease human hippocampus
Nguyen, H. D., Kim, W.-K., & Vu, G. H. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111930 · Cited by 17 · see citing works
Guan, P.-P., & Wang, P. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03277-z · Cited by 15 · see citing works
Moore, K., Sengupta, U., Puangmalai, N., Bhatt, N. N., & Kayed, R. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03211-3 · Cited by 14 · see citing works
Self-citationInternalization of extracellular Tau oligomers in Alzheimer’s disease
Chinnathambi, S., Rangappa, N., & Chandrashekar, M. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.01.005 · Cited by 14 · see citing works
Oligodendrocyte Dysfunction in Tauopathy: A Less Explored Area in Tau-Mediated Neurodegeneration
Majumder, M., & Dutta, D. (2024) · Cells · doi:10.3390/cells13131112 · Cited by 13 · see citing works
Excess Ub-K48 Induces Neuronal Apoptosis in Alzheimer’s Disease
Li, Q., Yuan, Y., Huang, S., Di, G., Chen, H., Zhuang, Y., Fang, W., Huang, Y., Tao, Y., Jiang, J., et al. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2312223 · Cited by 12 · see citing works
Abdel-Lah, E. S., Sherkawy, H. S., Mohamed, W. H., Fawy, M. A., Hasan, A. A., Muhammed, A. A., Taha, A. F., Tony, A. A., Hamad, N., & Gamea, M. G. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01755-5 · Cited by 12 · see citing works
Calcineurin inhibition prevents synaptic plasticity deficit induced by brain-derived tau oligomers
Scaduto, P., Marcatti, M., Bhatt, N. N., Kayed, R., & Taglialatela, G. (2024) · Brain Communications · doi:10.1093/braincomms/fcae277 · Cited by 11 · see citing works
Self-citationThe interactome of tau phosphorylated at T217 in Alzheimer’s disease human brain tissue
Kavanagh, T., Thierry, M., Balcomb, K., Ponce, J., Kanshin, E., Tapia-Sealey, A., Halliday, G. M., Ueberheide, B. M., Wısnıewskı, T., & Drummond, E. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02881-8 · Cited by 10 · see citing works
Targeting tau in Alzheimer’s Disease: rationale, approach and challenges
Aslanyan, A., Foiani, M. S., Giovannucci, T. A., McDade, E., Duff, K., Mummery, C. J., Schöll, M., Wildsmith, K. R., & Paterson, R. W. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00925-5 · Cited by 10 · see citing works
Arar, S. H., Haque, M. A., Bhatt, N. N., Zhao, Y., & Kayed, R. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00614 · Cited by 9 · see citing works
Self-citationRusu, D. B., Murariu, D., Gheorghita, R. E., & Graur, M. (2024) · Plants · doi:10.3390/plants13192764 · Cited by 7 · see citing works
Li, X., Ba, Z., Huang, J., Chen, J., Jiang, J., Huang, N., & Luo, Y. (2024) · Ibrain · doi:10.1002/ibra.12176 · Cited by 7 · see citing works
Sengupta, U., & Kayed, R. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3629-9_9 · Cited by 7 · see citing works
Self-citationMarcatti, M., Tumurbaatar, B., Zhang, W. R., Scaduto, P., Guptarak, J., Kadamangudi, S., Schuetze, R., Fracassi, A., Kayed, R., & Taglialatela, G. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70550 · Cited by 6 · see citing works
Self-citationUntangling the Complexity and Impact of Tau Protein Ubiquitination
Trivellato, D., Munari, F., Assfalg, M., Capaldi, S., & D’Onofrio, M. (2024) · ChemBioChem · doi:10.1002/cbic.202400566 · Cited by 6 · see citing works
Abiose, O., Rutledge, J., Losada, P. M., Belloy, M. E., Wilson, E. N., He, Z., Trelle, A. N., Channappa, D., Romero, A., Park, J., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13576 · Cited by 6 · see citing works
Bhatt, N. N., Puangmalai, N., Sengupta, U., Jerez, C., Kidd, M., Gandhi, S. S., & Kayed, R. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.105628 · Cited by 5 · see citing works
Self-citationZhang, Y., Wu, J., You, G., Guo, W., Wang, Y., Yu, Z., Geng, Y., Zhong, Q., Zan, J., & Zheng, L. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2206138 · Cited by 4 · see citing works
Inhibition of UBE2N promotes the clearance of mutant HTT (huntingtin) in HD knock-in mice
Ou, K., Wang, X., Guo, M., Li, D., Zhang, C., Chen, L., Hou, J., Jia, Q., Zhu, L., Yang, S., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2549109 · Cited by 3 · see citing works
Shabana, S., Hamouda, H. I., Shang, A., Shao, S., Zhao, J., Yuan, H., & Liu, B. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01932-2 · Cited by 3 · see citing works
Post-translational modifications as a regulatory code for tau function in health and disease
Nordbeck, A. J., Sharma, B., Garcia, C. A., & Tseng, J. (2026) · Frontiers in Dementia · doi:10.3389/frdem.2026.1834737 · Cited by 3 · see citing works
UBE3A: Bridging the gap between neurodevelopment, neural function, and neurodegenerative woes
Nash, K. R., Jinwal, U. K., & Bhat, K. M. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241283680 · Cited by 3 · see citing works
Santiago-Ruiz, A. N., Hugelier, S., Correa, G. L., Bond, C., Lee, E. B., & Lakadamyali, M. (2025) · Advanced Science · doi:10.1002/advs.202509773 · Cited by 3 · see citing works
Vanparys, A., Balty, C., Johanns, M., Zola, N. K. N., Herinckx, G., Calsteren, M. V., Suelves, N., Woodard, J. L., Vertommen, D., Kienlen‐Campard, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.10.717615 · Cited by 3 · see citing works
Haque, M. A., Montalbano, M., Khan, S., Puangmalai, N., Bhatt, N. N., Shchankin, N., Jerez, C., & Kayed, R. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167995 · Cited by 2 · see citing works
Self-citationMolecular and environmental drivers of tau post-translational modifications and tau pathology
Price, T. M., Tucker, A. E., & Funk, K. E. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103223 · Cited by 2 · see citing works
Arar, S. H., Haque, M. A., Kayed, A., Khan, S., Bhatt, N. N., Zhao, Y., & Kayed, R. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00122 · Cited by 1 · see citing works
Self-citationInteracting partners of Tau protein in Alzheimer’s disease
Chinnathambi, S., Velmurugan, G., Kumarappan, M., & Chandrashekar, M. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.10.005 · Cited by 1 · see citing works
Ubiquitin signatures on aggregating proteins in neurodegeneration
Sahoo, S., Padhy, A. A., Shivani, K., Misra, A., & Mishra, P. (2025) · Essays in Biochemistry · doi:10.1042/ebc20253046 · Cited by 1 · see citing works
Senapati, S., Sciortino, A., Samples, M., Shchankin, N., Aday, A., Zhao, Y., Montalbano, M., & Kayed, R. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00033-0 · Cited by 1 · see citing works
Self-citationOosterlynck, M., Fichter, L., Leroux, É., Eddarkaoui, S., Bouillet, T., Lefebvre, C., Nguyen, M., Maurage, C., Accart, B., Dupré, E., et al. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-026-01250-1 · Cited by 1 · see citing works
Soto‐Díaz, K., Varfolomeev, E. E., & Vucic, D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00198-8
Regional correlates of tau pathology and synaptic function in primary age-related tauopathy
Kadamangudi, S., Sánchez-Sánchez, L., Limón, A., & Taglialatela, G. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261416524
Tian, S., Zong, W., Zeng, Z., Wang, J., Niu, Q., Zhang, S., Zhang, H., & Li, B. (2026) · BioMed Research International · doi:10.1155/bmri/8877510
Tracking Tau Multimerization in the Adult Drosophila Brain
Chinchankar, M. N., & Frost, B. E. (2026) · Neuromethods · doi:10.1007/978-1-0716-5234-3_14
Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies
Puangmalai, N., Bhatt, N. N., Suthprasertporn, N., Miranda-Morales, E. G., Shchankin, N., Samples, M., Balci, A. E., Liew, J. Y., Montalbano, M., Zhao, Y., et al. (2026) · The EMBO Journal · doi:10.1038/s44318-026-00897-8
Self-citationThe Function of Tau in Astrocytes: Advantage or Damage
Luis-Hernández, K. G., Beltrán‐Parrazal, L., Morgado‐Valle, C., López‐Meraz, M. L., García, L. I., & Chi-Castañeda, D. (2026) · Neuroglia · doi:10.3390/neuroglia7030030
From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer’s disease
Miao, J., Xue, C., Yan, X., Gu, J., Chu, D., & Sun, H. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1927017
Yanamandra, K., Romanul, N., Patel, H., Sanders, H., Chang, R., Darcy, A., Brown, N., Kane, C. A., Wu, H.-Y., Jagtap, K., et al. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00049-6
Bisht, A., Pippadpally, S., & Kumar, V. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06310-z
- Authors
- Puangmalai, N., Sengupta, U., Bhatt, N., Gaikwad, S., Montalbano, M., Bhuyan, A., Garcia, S., McAllen, S., Sonawane, M., Jerez, C., Zhao, Y., & Kayed, R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Kayed, Rakez
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 298
- Issue
- 4
- Pages
- 101766
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC8942844
- OpenAlex
- W4212950915
- Cited by
- 68
- References
- 91
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 24 · 2023: 12 · 2022: 5
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association Inc
- NIH
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau oligomers, Alzheimer's disease, tauopathy, tau aggregation, seeding activity, proteasome dysfunction, lysosomal dysfunction, cell survival pathways
- MeSH terms
- Alzheimer Disease, Cells, Cultured, Humans, Lysine, Neurons, tau Proteins, Tauopathies, Ubiquitin, Ubiquitination
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