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Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin
Open accessAbstract
Mislocalization and aggregation of Aβ and Tau combined with loss of synapses and microtubules (MTs) are hallmarks of Alzheimer disease. We exposed mature primary neurons to Aβ oligomers and analysed changes in the Tau/MT system. MT breakdown occurs in dendrites invaded by Tau (Tau missorting) and is mediated by spastin, an MT-severing enzyme. Spastin is recruited by MT polyglutamylation, induced by Tau missorting triggered translocalization of TTLL6 (Tubulin-Tyrosine-Ligase-Like-6) into dendrites. Consequences are spine loss and mitochondria and neurofilament mislocalization. Missorted Tau is not axonally derived, as shown by axonal retention of photoconvertible Dendra2-Tau, but newly synthesized. Recovery from Aβ insult occurs after Aβ oligomers lose their toxicity and requires the kinase MARK (Microtubule-Affinity-Regulating-Kinase). In neurons derived from Tau-knockout mice, MTs and synapses are resistant to Aβ toxicity because TTLL6 mislocalization and MT polyglutamylation are prevented; hence no spastin recruitment and no MT breakdown occur, enabling faster recovery. Reintroduction of Tau re-establishes Aβ-induced toxicity in TauKO neurons, which requires phosphorylation of Tau's KXGS motifs. Transgenic mice overexpressing Tau show TTLL6 translocalization into dendrites and decreased MT stability. The results provide a rationale for MT stabilization as a therapeutic approach.
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“Thus, cultured neurons from tau knockout (Tau−/−) mice are not susceptible to Aβ-induced synaptic damage and neurotoxicity (Rapoport et al., 2002; Nussbaum et al., 2012; Zempel et al., 2013) or to Aβ-induced defects in axonal transport (Vossel et al., 2011).”
From Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice (2017) · cites this paper as Zempel et al., 2013
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“In primary neurons, we further observed that CIP2A promoted tau translocalization to dendrites and spines, which is considered to be the key event mediating the synaptic toxicity of tau (Pooler et al., 2014; Zempel et al., 2013).”
From CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease (2018) · cites this paper as Zempel et al., 2013
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Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 2×
“In the present study, we focussed on the link between A b O and the neuronal cytoskeleton, notably the phosphorylation/ missorting of Tau and breakdown of MTs because these features are early hallmarks of AD (Braak and Braak, 1991; Spires-Jones et al , 2009).”
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188 · cited 1×
“In familial AD, genetic evidence points to a master role of A b aggregation, leading to downstream events including Tau hyperphosphorylation and aggregation (Haass and Selkoe, 2007; Karran et al , 2011).”
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821
Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 4×
“This is indeed the case, since blockage of both global and Tau protein synthesis strongly reduces dendritic missorting of Tau after A b O exposure.”
InfluentialCellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009) · Nature · doi:10.1038/nature07761 · Cited by 1,560
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Bloom (2014) · doi:10.1001/jamaneurol.2013.5847 · Cited by 2,194
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
Spires-Jones, T. L., & Hyman, B. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.004 · Cited by 1,201
Fricker, M., Tolkovsky, A. M., Borutaitė, V., Coleman, M. P., & Brown, G. C. (2018) · Physiological Reviews · doi:10.1152/physrev.00011.2017 · Cited by 1,148
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
Stress granules and neurodegeneration
Wolozin, B., & Ivanov, P. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0222-5 · Cited by 810
Building the Neuronal Microtubule Cytoskeleton
Kapitein, L. C., & Hoogenraad, C. C. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.046 · Cited by 684
Epileptic activity in Alzheimer’s disease: Causes and clinical relevance
Vossel, K. A., Tartaglia, M. C., Nygaard, H. B., Zeman, A. Z., & Miller, B. L. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30044-3 · Cited by 590
Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies
Nasica-Labouze, J., Nguyen, P. H., Sterpone, F., Berthoumieu, O., Buchete, N., Côté, S., Simone, A. D., Doig, A. J., Faller, P., García, A. E., et al. (2015) · Chemical Reviews · doi:10.1021/cr500638n · Cited by 591
Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.014 · Cited by 517
Synaptic degeneration in Alzheimer disease
Tzioras, M., McGeachan, R. I., Durrant, C. S., & Spires-Jones, T. L. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-022-00749-z · Cited by 504
Tau imaging: early progress and future directions
Villemagne, V. L., Fodero-Tavoletti, M. T., Masters, C. L., & Rowe, C. C. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70252-2 · Cited by 501
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
Kent, S. A., Spires-Jones, T. L., & Durrant, C. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02196-w · Cited by 446
Systemic administration of epothilone B promotes axon regeneration after spinal cord injury
Ruschel, J., Hellal, F., Flynn, K. C., Dupraz, S., Elliott, D. A., Tedeschi, A., Bates, M., Sliwinski, C., Brook, G. A., Dobrindt, K., et al. (2015) · Science · doi:10.1126/science.aaa2958 · Cited by 444
Tau Protein Modifications and Interactions: Their Role in Function and Dysfunction
Mietelska‐Porowska, A., Wasik, U., Goras, M., Filipek, A., & Niewiadomska, G. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15034671 · Cited by 431
Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies
Polanco, J. C., Li, C., Bodea, L., Martínez‐Mármol, R., Meunier, F. A., & Götz, J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.162 · Cited by 386
Ferreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00191 · Cited by 373
Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity
Vanderweyde, T. E., Apicco, D. J., Youmans-Kidder, K., Ash, P. E. A., Cook, C. N., da Rocha, E. L., Jansen‐West, K. R., Frame, A. A., Citro, A., Leszyk, J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.045 · Cited by 346
Molecular Basis of Familial and Sporadic Alzheimer's Disease
Dorszewska, J., Prendecki, M., Oczkowska, A., Dezor, M., & Kozubski, W. P. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160314150501 · Cited by 340
Sadleir, K. R., Kandalepas, P. C., Buggia-Prévot, V., Nicholson, D. A., Thinakaran, G., & Vassar, R. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1558-9 · Cited by 294
Dendritic Tau in Alzheimer’s Disease
Ittner, A., & Ittner, L. M. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.003 · Cited by 278
Stability properties of neuronal microtubules
Baas, P. W., Rao, A. N., Matamoros, A. J., & Leo, L. (2016) · Cytoskeleton · doi:10.1002/cm.21286 · Cited by 315
Izzo, N. J., Xu, J., Zeng, C., Kirk, M. J., Mozzoni, K., Silky, C., Rehak, C., Yurko, R., Look, G., Rishton, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111899 · Cited by 157
A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration
Walsh, D. M., & Selkoe, D. J. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.13 · Cited by 301
Lost after translation: missorting of Tau protein and consequences for Alzheimer disease
Zempel, H., & Mandelkow�, E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.004 · Cited by 284
Graded Control of Microtubule Severing by Tubulin Glutamylation
Valenstein, M. L., & Roll‐Mecak, A. (2016) · Cell · doi:10.1016/j.cell.2016.01.019 · Cited by 268
Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies
Chen, Y., Fu, A. K. Y., & Ip, N. Y. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.11.006 · Cited by 258
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201
Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease
Pereira, J. B., Janelidze, S., Ossenkoppele, R., Kvartsberg, H., Brinkmalm, A., Mattsson, N., Stomrud, E., Smith, R. A., Zetterberg, H., Blennow, K., et al. (2020) · Brain · doi:10.1093/brain/awaa395 · Cited by 208
Amyloid-β and Tau at the Crossroads of Alzheimer’s Disease
Gallardo, G., & Holtzman, D. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9358-8_16 · Cited by 212
Yau, K. W., Schätzle, P., Tortosa, E., Pagès, S., Holtmaat, A. J. D. G., Kapitein, L. C., & Hoogenraad, C. C. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2430-15.2016 · Cited by 194
Goure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt272 · Cited by 190
Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles
Guix, F. X., Corbett, G. T., Cha, D., Mustapić, M., Liu, W., Mengel, D., Chen, Z., Aïkawa, E., Young‐Pearse, T. L., Kapogiannis, D., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030663 · Cited by 186
Izzo, N. J., Staniszewski, A., To, L., Fa, M., Teich, A. F., Saeed, F., Wostein, H., Walko, T., Vaswani, A., Wardius, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111898 · Cited by 180
Li, C., & Götz, J. (2017) · The EMBO Journal · doi:10.15252/embj.201797724 · Cited by 178
Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease
Sun, Y., Ma, C., Sun, H. J., Wang, H., Wei, P., Zhou, Z., Wang, H., Pi, C., Shi, Y., & He, X. (2020) · Journal of Diabetes Research · doi:10.1155/2020/4981814 · Cited by 181
Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β
Vossel, K. A., Xu, J. C., Fomenko, V., Miyamoto, T., Suberbielle, E., Knox, J. A., Ho, K., Kim, D. H., Yu, G.-Q., & Mucke, L. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201407065 · Cited by 167
Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro
Rane, J. S., Bhaumik, P., & Panda, D. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170351 · Cited by 169
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
Oligomer Formation of Tau Protein Hyperphosphorylated in Cells
Tepper, K., Biernat, J., Kumar, S., Wegmann, S., Timm, T., Hübschmann, S., Redecke, L., Mandelkow, E., Müller, D. J., & Mandelkow�, E. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.611368 · Cited by 159
Hall, A., Throesch, B. T., Buckingham, S. C., Markwardt, S. J., Peng, Y., Wang, Q., Hoffman, D., & Roberson, E. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2552-14.2015 · Cited by 152
SIRT1 Deacetylates Tau and Reduces Pathogenic Tau Spread in a Mouse Model of Tauopathy
Min, S., Sohn, P., Li, Y., Devidze, N., Johnson, J. R., Krogan, N. J., Masliah, E., Mok, S., Gestwicki, J. E., & Gan, L. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2369-17.2018 · Cited by 151
UB‐311, a novel UBITh ® amyloid β peptide vaccine for mild Alzheimer's disease
Wang, C. Y., Wang, P., Chiu, M., Finstad, C. L., Lin, F., Lynn, S., Tai, Y., De Fang, X., Zhao, K., Hung, C., et al. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.03.005 · Cited by 150
Schützmann, M. P., Hasecke, F., Bachmann, S., Zielinski, M., Hänsch, S., Schroeder, G. F., Zempel, H., & Hoyer, W. (2021) · Nature Communications · doi:10.1038/s41467-021-24900-4 · Cited by 152
Zempel, H., Dennissen, F. J. A., Kumar, Y., Luedtke, J., Biernat, J., Mandelkow, E., & Mandelkow�, E. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.784702 · Cited by 147
Buchholz, S., & Zempel, H. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13784 · Cited by 154
Microtubules in health and degenerative disease of the nervous system
Matamoros, A. J., & Baas, P. W. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.06.016 · Cited by 137
Pagano, K., Tomaselli, S., Molinari, H., & Ragona, L. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.619667 · Cited by 139
Derisbourg, M. J., Leghay, C., Chiappetta, G., Fernández-Gómez, F.-J., Laurent, C., Demeyer, D., Carrier, S., Buée‐Scherrer, V., Blum, D. L., Vinh, J., et al. (2015) · Scientific Reports · doi:10.1038/srep09659 · Cited by 149
Miller, E. C., Teravskis, P. J., Dummer, B. W., Zhao, X., Huganir, R. L., & Liao, D. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12507 · Cited by 131
Microtubule Dysfunction: A Common Feature of Neurodegenerative Diseases
Sferra, A., Nicita, F., & Bertini, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197354 · Cited by 138
Savioz, A., Leuba, G., & Vallet, P. G. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.09.004 · Cited by 127
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114
Benseny‐Cases, N., Klementieva, O. L., Cotte, M., Ferrer, I., & Cladera, J. (2014) · Analytical Chemistry · doi:10.1021/ac502667b · Cited by 122
Shi, Z., Zhang, K., Zhou, H., Jiang, L., Xie, B., Wang, R., Xia, W., Yin, Y., Gao, Z., Cui, D., et al. (2020) · Aging Cell · doi:10.1111/acel.13125 · Cited by 115
Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma
Chiasseu, M., Vargas, J. L. C., Destroismaisons, L., Velde, C. V., Leclerc, N. M., & Polo, A. D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3986-15.2016 · Cited by 105
The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders
Eira, J., Silva, C. S., Sousa, M. M., & Liz, M. A. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.007 · Cited by 109
The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer′s Disease (AD)
Mroczko, B., Groblewska, M., & Litman‐Zawadzka, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194661 · Cited by 111
Ondrejčák, T., Klyubin, I. V., Corbett, G. T., Fraser, G. M., Hong, W., Mably, A. J., Gardener, M. J., Hammersley, J., Perkinton, M. S., Billinton, A., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1700-18.2018 · Cited by 110
Alzheimer's disease pathophysiology in the Retina
Gaire, B. P., Koronyo, Y., Fuchs, D.-T. S., Shi, H., Rentsendorj, A., Danziger, R., Vit, J., Mirzaei, N., Doustar, J., Sheyn, J., et al. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101273 · Cited by 107
Tubulin post‐translational modifications control neuronal development and functions
Moutin, M., Bosc, C., Peris, L., & Andrieux, A. (2020) · Developmental Neurobiology · doi:10.1002/dneu.22774 · Cited by 97
Cheng, J. S., Craft, R., Yu, G.-Q., Ho, K., Wang, X., Mohan, G., Mangnitsky, S., Ponnusamy, R., & Mucke, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115765 · Cited by 100
Brill, M. S., Kleele, T., Ruschkies, L., Wang, M., Marahori, N. A., Reuter, M. S., Hausrat, T. J., Weigand, E. E., Fisher, M., Ahles, A., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.049 · Cited by 105
Transport and diffusion of Tau protein in neurons
Scholz, T., & Mandelkow�, E. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1610-7 · Cited by 105
Kaniyappan, S., Chandupatla, R., Mandelkow, E., & Mandelkow, E. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.04.002 · Cited by 100
Axonal Degeneration in AD: The Contribution of Aβ and Tau
Salvadores, N., Gerónimo‐Olvera, C., & Court, F. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.581767 · Cited by 101
Zempel, H., & Mandelkow, E. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0064-1 · Cited by 100
CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease
Shentu, Y.-P., Huo, Y., Feng, X.-L., Gilbert, J., Zhang, Q., Liuyang, Z.-Y., Wang, X.-L., Wang, G., Zhou, H., Wang, X.-C., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.009 · Cited by 90
“In primary neurons, we further observed that CIP2A promoted tau translocalization to dendrites and spines, which is considered to be the key event mediating the synaptic toxicity of tau (Pooler et al., 2014; Zempel et al., 2013).”
BackgroundMicrotubule Dynamics in Neuronal Development, Plasticity, and Neurodegeneration
Penazzi, L., Bakota, L., & Brandt, R. (2015) · International review of cytology · doi:10.1016/bs.ircmb.2015.09.004 · Cited by 97
The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease
Sulistio, Y. A., & Heese, K. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-9063-4 · Cited by 93
Bell, M. J., & Zempel, H. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0152 · Cited by 92
Brandt, R., Trushina, N. I., & Bakota, L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590059 · Cited by 97
Xia, D., Li, C., & Götz, J. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.12.017 · Cited by 91
Justice, N. J., Huang, L., Tian, J.-B., Cole, A., Pruski, M., Hunt, A. J., Flores, R., Zhu, M. X., Arenkiel, B. R., & Zheng, H. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3333-14.2015 · Cited by 81
Do, T. D., Economou, N. J., Chamas, A., Buratto, S. K., Shea, J., & Bowers, M. T. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp506258g · Cited by 81
Zhao, Y., Chen, X., Wu, Y., Wang, Y., Li, Y., & Xiang, C. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00140 · Cited by 79
Kanno, T., Tsuchiya, A., & Nishizaki, T. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.034 · Cited by 76
Kobayashi, S., Tanaka, T., Soeda, Y., Almeida, O. F. X., & Takashima, A. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.05.012 · Cited by 74
Structural basis for polyglutamate chain initiation and elongation by TTLL family enzymes
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Metadata
- Authors
- Zempel, H., Luedtke, J., Kumar, Y., Biernat, J., Dawson, H., Mandelkow, E., & Mandelkow, E.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Duke Medical Center (US)
- Center of Advanced European Studies and Research (DE)
- Corresponding author
- Mandelkow, Eva‐Maria
- Venue
- The EMBO Journal
- Published
- 2013-09-24
- Volume
- 32
- Issue
- 22
- Pages
- 2920-2937
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3831312
- OpenAlex
- W2122620510
- Cited by
- 283
- References
- 85
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 23 · 2023: 15 · 2022: 24 · 2021: 17 · 2020: 25 · 2019: 16 · 2018: 22 · 2017: 18 · 2016: 34 · 2015: 26 · 2014: 26 · 2013: 3
- FWCI
- 20.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Wellcome Trust (089703)
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta oligomers, tau protein, Alzheimer's disease, microtubule severing, spastin, synaptic damage, dendritic microtubules, MARK kinases, tau phosphorylation, synaptic loss, microtubule stabilization
- MeSH terms
- Spastin, Adenosine Triphosphatases, Animals, Cells, Cultured, Microtubules, Peptide Synthases, Synapses, Amyloid beta-Peptides, tau Proteins, Mice, Knockout, Glutamic Acid, Mice, Rats
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