Tau exacerbates excitotoxic brain damage in an animal model of stroke

Bi, Mian; Gladbach, Amadeus; van Eersel, Janet; Ittner, Arne; Przybyla, Magdalena; van Hummel, Annika; Chua, Sook Wern; van der Hoven, Julia; Lee, Wei S.; Müller, Julius; Parmar, Jasneet; Jonquieres, Georg von; Stefen, Holly; Guccione, Ernesto; Fath, Thomas; Housley, Gary D.; Klugmann, Matthias; Ke, Yazi D.; Ittner, Lars M.

doi:10.1038/s41467-017-00618-0

Cited by 167Neuroscience and Neuropharmacology ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Tau exacerbates excitotoxic brain damage in an animal model of stroke

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Bi, Mian, Gladbach, Amadeus, van Eersel, Janet, Ittner, Arne, Przybyla, Magdalena, van Hummel, Annika, Chua, Sook Wern, van der Hoven, Julia +11 more·2017·Nature Communications

DOI 10.1038/s41467-017-00618-0PMC PMC5589746

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Abstract

Neuronal excitotoxicity induced by aberrant excitation of glutamatergic receptors contributes to brain damage in stroke. Here we show that tau-deficient (tau −/− ) mice are profoundly protected from excitotoxic brain damage and neurological deficits following experimental stroke, using a middle cerebral artery occlusion with reperfusion model. Mechanistically, we show that this protection is due to site-specific inhibition of glutamate-induced and Ras/ERK-mediated toxicity by accumulation of Ras-inhibiting SynGAP1, which resides in a post-synaptic complex with tau. Accordingly, reducing SynGAP1 levels in tau −/− mice abolished the protection from pharmacologically induced excitotoxicity and middle cerebral artery occlusion-induced brain damage. Conversely, over-expression of SynGAP1 prevented excitotoxic ERK activation in wild-type neurons. Our findings suggest that tau mediates excitotoxic Ras/ERK signaling by controlling post-synaptic compartmentalization of SynGAP1.

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These same mechanisms may render neurons vulnerable to excitotoxicity, as tau-dependent Fyn-PSD-95-NMDAR coupling amplifies glutamate receptor activation under pathological conditions.
“However, these same mechanisms may render neurons vulnerable to excitotoxicity, as tau-dependent Fyn-PSD-95-NMDAR coupling amplifies glutamate receptor activation under pathological conditions [52, 124].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [124]
The Results (‘Tau−/− mice lack excitotoxic Ras/ERK activation’; page unavailable) show that tau promotes excitotoxic signaling downstream of NMDA receptors, and the NMDA-infusion results show greater damage in mice with tau. The Discussion links tau loss to reduced synaptic Fyn, but the paper does not establish that Fyn–PSD-95–NMDAR coupling amplifies glutamate receptor activation; its demonstrated mechanism centers on SynGAP1 and downstream Ras/ERK signaling. (LLM, conf=0.86)
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Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · see citing works
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 · see citing works
Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke
Hacke, W., Kaste, M., Bluhmki, E., Brozman, M., Dávalos, A., Guidetti, D., Larrue, V., Lees, K. R., Medeghri, Z., Machnig, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804656 · Cited by 6,684 · see citing works
A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke
Berkhemer, O. A., Fransen, P. S. S., Beumer, D., van den Berg, L. A., Lingsma, H. F., Yoo, A. J., Schonewille, W. J., Vos, J. A., Nederkoorn, P. J., Wermer, M. J. H., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1411587 · Cited by 6,674 · see citing works
Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection
Campbell, B. C. V., Mitchell, P. J., Kleinig, T. J., Dewey, H. M., Churilov, L. P., Yassi, N., Yan, B., Dowling, R., Parsons, M. W., Oxley, T. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414792 · Cited by 5,830 · see citing works
KEGG for integration and interpretation of large-scale molecular data sets
Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., & Tanabe, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr988 · Cited by 4,848 · see citing works
Endovascular Stroke Therapy Results Improve over Time: The ‘Learning Curve' at a New Comprehensive Stoke Center
Benardete, E. A., & Nair, A. K. (2015) · Cerebrovascular Diseases Extra · doi:10.1159/000370060 · Cited by 2,546 · see citing works
Treatment Strategies for Acute Ischemic Stroke Caused by Carotid Artery Occlusion
Li, W., Yin, Q., Xu, G., & Liu, X. (2016) · Interventional Neurology · doi:10.1159/000445304 · Cited by 2,319 · see citing works
Stroke
Donnan, G. A., Fisher, M., Macleod, M. R., & Davis, S. M. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60694-7 · Cited by 2,231 · 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
Intra-Arterial Mechanical Thrombectomy: An Effective Treatment for Ischemic Stroke Caused by Endocarditis
Sveinsson, O. A., Herrman, L., & Holmin, S. (2016) · Case Reports in Neurology · doi:10.1159/000452213 · Cited by 2,037 · see citing works
Negative Fluid-Attenuated Inversion Recovery- Based Intravenous Thrombolysis Using Recombinant Tissue Plasminogen Activator in Acute Stroke Patients with Unknown Onset Time
Aoki, J., Kimura, K., Shibazaki, K., & Sakamoto, Y. (2013) · Cerebrovascular Diseases Extra · doi:10.1159/000348552 · Cited by 1,929 · see citing works
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 · see citing works
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 · see citing works
Self-citation
Blockade of N -Methyl-D-Aspartate Receptors May Protect Against Ischemic Damage in the Brain
Simon, R. P., Swan, J. H., Griffiths, T., & Meldrum, B. S. (1984) · Science · doi:10.1126/science.6093256 · Cited by 1,682 · see citing works
A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke
Kidwell, C. S., Jahan, R., GORNBEIN, J. A., Alger, J. R., Nenov, V., Ajani, Z. A., Feng, L., Meyer, B. C., Olson, S. E., Schwamm, L. H., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1212793 · Cited by 1,381 · see citing works
Tau proteins of alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms
Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,114 · see citing works
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106 · see citing works
Treatment of Ischemic Brain Damage by Perturbing NMDA Receptor- PSD-95 Protein Interactions
Aarts, M. M., Liu, Y., Liu, L., Besshoh, S., Arundine, M., Gurd, J. W., Wang, Y.-T., Salter, M. W., & Tymianski, M. (2002) · Science · doi:10.1126/science.1072873 · Cited by 998 · see citing works
Acute ischemic stroke: Overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia
Durukan, A., & Tatlisumak, T. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.04.015 · Cited by 733 · see citing works
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2646 · Cited by 687 · see citing works
Excitotoxicity: Bridge to various triggers in neurodegenerative disorders
Mehta, A., Prabhakar, M., Kumar, P., Deshmukh, R. R., & Sharma, P. L. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.10.032 · Cited by 662 · see citing works
Molecular Mechanisms of Ischemia–Reperfusion Injury in Brain: Pivotal Role of the Mitochondrial Membrane Potential in Reactive Oxygen Species Generation
Sanderson, T. H., Reynolds, C. A., Kumar, R., Przyklenk, K., & Hüttemann, M. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8344-z · Cited by 640 · see citing works
SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family
Kim, J. H., Liao, D., Lau, L.-F., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)81008-9 · Cited by 634 · see citing works
A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II
Chen, H.-J., Rojas-Soto, M., Oguni, A., & Kennedy, M. B. (1998) · Neuron · doi:10.1016/s0896-6273(00)80471-7 · Cited by 590 · see citing works
Neurotrophins are required for nerve growth during development
Tucker, K. L., Meyer, M., & Barde, Y. (2001) · Nature Neuroscience · doi:10.1038/82868 · Cited by 526 · see citing works
Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking
Kim, M. J., Dunah, A. W., Wang, Y. T., & Sheng, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.031 · Cited by 494 · see citing works
A role for the Ras signalling pathway in synaptic transmission and long-term memory
Brambilla, R., Gnesutta, N., Minichiello, L., White, G., Roylance, A. J., Herron, C. E., Ramsey, M., Wolfer, D. P., Cestari, V., Rossi‐Arnaud, C., et al. (1997) · Nature · doi:10.1038/36849 · Cited by 471 · see citing works
The NMDA Receptor Is Coupled to the ERK Pathway by a Direct Interaction between NR2B and RasGRF1
Krapivinsky, G. B., Krapivinsky, L., Manasian, Y., Ivanov, A., Tyzio, R., Pellegrino, C., Ben‐Ari, Y., Clapham, D. E., & Medina, I. (2003) · Neuron · doi:10.1016/s0896-6273(03)00645-7 · Cited by 431 · see citing works
Treatment of Acute Ischemic Stroke
Brott, T. G., & Bogousslavsky, J. (2000) · New England Journal of Medicine · doi:10.1056/nejm200009073431007 · Cited by 397 · see citing works
Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses
Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.045 · Cited by 385 · see citing works
Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia
Namura, S., Iihara, K., Takami, S., Nagata, I., Kikuchi, H., Matsushita, K., Moskowitz, M. A., Bonventre, J. V., & Alessandrini, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181213498 · Cited by 360 · see citing works
Mutations in SYNGAP1 in Autosomal Nonsyndromic Mental Retardation
Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Côté, M., Perreau-Linck, E., Carmant, L., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805392 · Cited by 336 · see citing works
Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal‐regulated kinases (ERK) activity in cultured rat hippocampal neurons
Ivanov, A., Pellegrino, C., Rama, S., Dumalska, I., Salyha, Y. T., Ben‐Ari, Y., & Medina, I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.105510 · Cited by 320 · see citing works
SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation
Krapivinsky, G., Medina, I., Krapivinsky, L., Gapon, S., & Clapham, D. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.003 · Cited by 287 · see citing works
TTC, Fluoro-Jade B and NeuN staining confirm evolving phases of infarction induced by middle cerebral artery occlusion
Liu, F., Schafer, D. P., & McCullough, L. D. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.12.028 · Cited by 286 · see citing works
Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes
Nichols, R. A., Sihra, T. S., Czernik, A. J., Nairn, A. C., & Greengard, P. (1990) · Nature · doi:10.1038/343647a0 · Cited by 283 · see citing works
Interaction of Endogenous Tau Protein with Synaptic Proteins Is Regulated by N-Methyl-d-aspartate Receptor-dependent Tau Phosphorylation*
Mondragón-Rodríguez, S., Trillaud-Doppia, E., Dudilot, A., Bourgeois, C., Lauzon, M., Leclerc, N., & Boehm, J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.401240 · Cited by 272 · see citing works
Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP
Araki, Y., Zeng, M., Zhang, M., & Huganir, R. L. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.023 · Cited by 271 · see citing works
Mutations inSYNGAP1Cause Intellectual Disability, Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency
Berryer, M. H., Hamdan, F. F., Klitten, L. L., Møller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., et al. (2013) · Human Mutation · doi:10.1002/humu.22248 · Cited by 266 · see citing works
Site-specific phosphorylation of tau inhibits amyloid-β toxicity in Alzheimer’s mice
Ittner, A., Chua, S. W., Bertz, J., Volkerling, A., van der Hoven, J., Gladbach, A., Przybyla, M., Bi, M., van Hummel, A., Stevens, C. H., et al. (2016) · Science · doi:10.1126/science.aah6205 · Cited by 263 · see citing works
Self-citation
Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging
Yasuda, R., Harvey, C. D., Zhong, H., Sobczyk, A., Aelst, L. V., & Svoboda, K. (2006) · Nature Neuroscience · doi:10.1038/nn1635 · Cited by 261 · see citing works
SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
Rumbaugh, G., Adams, J. P., Kim, J. H., & Huganir, R. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600084103 · Cited by 260 · see citing works
Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls
Liu, F., & McCullough, L. D. (2011) · BioMed Research International · doi:10.1155/2011/464701 · Cited by 256 · see citing works
Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse and Drosophila Genetic Models of Epilepsy
Holth, J. K., Bomben, V. C., Reed, J. G., Inoue, T., Younkin, L., Younkin, S. G., Pautler, R. G., Botas, J., & Noebels, J. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3191-12.2013 · Cited by 238 · see citing works
Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome
Osterweil, E. K., Chuang, S.-C., Chubykin, A. A., Sidorov, M., Bianchi, R., Wong, R. K. S., & Bear, M. F. (2013) · Neuron · doi:10.1016/j.neuron.2012.01.034 · Cited by 230 · see citing works
Procedural and Strain-related Variables Significantly Affect Outcome in a Murine Model of Focal Cerebral Ischemia
Connolly, E. S., Winfree, C. J., Stern, D. M., Stern, D. M., Solomon, R. A., & Pinsky, D. J. (1996) · Neurosurgery · doi:10.1097/00006123-199603000-00021 · Cited by 227 · see citing works
Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia
Ittner, L. M., Fath, T., Ke, Y. D., Bi, M., van Eersel, J., Li, K. M., Gunning, P. W., & Götz, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808084105 · Cited by 219 · see citing works
Self-citation
Neuronal Damage and Plasticity Identified by Microtubule-Associated Protein 2, Growth-Associated Protein 43, and Cyclin D1 Immunoreactivity After Focal Cerebral Ischemia in Rats
Li, Y., Jiang, N., Powers, C., & Chopp, M. (1998) · Stroke · doi:10.1161/01.str.29.9.1972 · Cited by 218 · see citing works
Primary support cultures of hippocampal and substantia nigra neurons
Fath, T., Ke, Y. D., Gunning, P. W., Götz, J., & Ittner, L. M. (2008) · Nature Protocols · doi:10.1038/nprot.2008.199 · Cited by 210 · see citing works
Self-citation
SynGAP regulates spine formation
Vazquez, L. E., Chen, H.-J., Sokolova, I., Knuesel, I., & Kennedy, M. B. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3213-04.2004 · Cited by 203 · see citing works
NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynaptic receptors
Zhou, X., Hollern, D. P., Liao, J., Andrechek, E. R., & Wang, H. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.82 · Cited by 200 · see citing works
Lack of Tau Proteins Rescues Neuronal Cell Death and Decreases Amyloidogenic Processing of APP in APP/PS1 Mice
Leroy, K., Ando, K., Laporte, V., Dedecker, R., Suain, V., Authelet, M., Héraud, C., Pierrot, N., Yilmaz, Z., Octave, J.-N., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.08.012 · Cited by 161 · see citing works
Phosphorylated Tau Interacts with c-Jun N-terminal Kinase-interacting Protein 1 (JIP1) in Alzheimer Disease
Ittner, L. M., Ke, Y. D., & Götz, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014472 · Cited by 156 · see citing works
Self-citation
Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein
Wen, Y., Yang, S., Liu, R., & Simpkins, J. W. (2004) · Brain Research · doi:10.1016/j.brainres.2004.05.106 · Cited by 147 · see citing works
Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice
Palop, J. J., Chin, J., Bien‐Ly, N., Massaro, C. M., Yeung, B. Z., Yu, G.-Q., & Mucke, L. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2829-05.2005 · Cited by 144 · see citing works
Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats
Wen, Y., Yang, S., Liu, R., Brun-Zinkernagel, A. M., Koulen, P., & Simpkins, J. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311768200 · Cited by 141 · see citing works
Occurrence of nonconvulsive seizures, periodic epileptiform discharges, and intermittent rhythmic delta activity in rat focal ischemia
Hartings, J. A., Williams, A. J., & Tortella, F. C. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(02)00013-4 · Cited by 136 · see citing works
Glial promoter selectivity following AAV-delivery to the immature brain
von Jonquieres, G., Mersmann, N., Klugmann, C. B., Harasta, A. E., Lutz, B., Teahan, O., Housley, G. D., Fröhlich, D., Krämer-Albers, E.-M., & Klugmann, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065646 · Cited by 133 · see citing works
Self-citation
Lessons from Tau-Deficient Mice
Ke, Y. D., Suchowerska, A. K., van der Hoven, J., Silva, D. M. D., Wu, C. W., van Eersel, J., Ittner, A., & Ittner, L. M. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/873270 · Cited by 128 · see citing works
Self-citation
Tau‐targeted treatment strategies in Alzheimer's disease
Götz, J., Ittner, A., & Ittner, L. M. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01713.x · Cited by 127 · see citing works
Self-citation
Regulation of the Neuron-specific Ras GTPase-activating Protein, synGAP, by Ca2+/Calmodulin-dependent Protein Kinase II
Oh, J. S., Manzerra, P., & Kennedy, M. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314109200 · Cited by 118 · see citing works
Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-d-aspartate receptor antagonist MK-801
Gass, P., Spranger, M., Herdegen, T., Bravo, R., K�ck, P., Hacke, W., & Kiessling, M. (1992) · Acta Neuropathologica · doi:10.1007/bf00304474 · Cited by 103 · see citing works
Septal Glucagon-Like Peptide 1 Receptor Expression Determines Suppression of Cocaine-Induced Behavior
Harasta, A. E., Power, J., von Jonquières, G., Karl, T., Drucker, D. J., Housley, G. D., Schneider, M., & Klugmann, M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.47 · Cited by 91 · see citing works
Self-citation
Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study
Dewar, D., & Dawson, D. A. (1995) · Brain Research · doi:10.1016/0006-8993(95)00417-o · Cited by 88 · see citing works
Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia
Geddes, J. W., Schwab, C., Craddock, S. D., Wilson, J. L., & Pettigrew, L. C. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.69 · Cited by 83 · see citing works
Nonredundant Functions for Ras GTPase-Activating Proteins in Tissue Homeostasis
King, P. D., Lubeck, B. A., & Lapinski, P. E. (2013) · Science Signaling · doi:10.1126/scisignal.2003669 · Cited by 80 · see citing works
Short-term suppression of A315T mutant human TDP-43 expression improves functional deficits in a novel inducible transgenic mouse model of FTLD-TDP and ALS
Ke, Y. D., van Hummel, A., Stevens, C. H., Gladbach, A., Ippati, S., Bi, M., Lee, W. S., Krüger, S., van der Hoven, J., Volkerling, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1486-0 · Cited by 77 · see citing works
Self-citation
p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer’s disease
Ittner, A., Gladbach, A., Bertz, J., Suh, L. S., & Ittner, L. M. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0149-z · Cited by 77 · see citing works
Self-citation
Phosphorylation of Synaptic GTPase-activating Protein (synGAP) by Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) and Cyclin-dependent Kinase 5 (CDK5) Alters the Ratio of Its GAP Activity toward Ras and Rap GTPases
Walkup, W. G., Washburn, L. R., Sweredoski, M. J., Carlisle, H. J., Graham, R. L., Hess, S. Y., & Kennedy, M. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.614420 · Cited by 77 · see citing works
Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP
Muhia, M., Yee, B. K., Feldon, J., Markopoulos, F., & Knuesel, I. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07079.x · Cited by 71 · see citing works
Calmodulin Kinase IV –dependent CREB activation is required for neuroprotection via NMDA receptor‐ PSD 95 disruption
Bell, K. F. S., Bent, R. J., Meese‐Tamuri, S., Ali, A., Forder, J. P., & Aarts, M. M. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12176 · Cited by 63 · see citing works
SynGAP moves out of the core of the postsynaptic density upon depolarization
Yang, Y., Tao-Cheng, J.-H., Reese, T. S., & Döṣemeci, A. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.061 · Cited by 57 · see citing works
Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain
Xue, S., Gong, H., Jiang, T., Luo, W., Meng, Y., Liu, Q., Chen, S., & Li, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088067 · Cited by 53 · see citing works
The N-Terminal Extracellular Domain 23−60 of the Calcitonin Receptor-Like Receptor in Chimeras with the Parathyroid Hormone Receptor Mediates Association with Receptor Activity-Modifying Protein 1
Ittner, L. M., Koller, D., Muff, R., Fischer, J. A., & Born, W. (2005) · Biochemistry · doi:10.1021/bi048111o · Cited by 44 · see citing works
Self-citation
Phosphorylation of Histone H2A.X as an Early Marker of Neuronal Endangerment following Seizures in the Adult Rat Brain
Crowe, S. L., Tsukerman, S., Gale, K., Jorgensen, T. J., & Kondratyev, A. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0092-11.2011 · Cited by 43 · see citing works
Differential Changes in Phosphorylation of Tau at PHF-1 and 12E8 Epitopes During Brain Ischemia and Reperfusion in Gerbils
Gordon‐Krajcer, W., Koźniewska, E., Łazarewicz, J. W., & Ksiȩżak-Reding, H. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9199-3 · Cited by 41 · see citing works
Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia
Morioka, M., Kawano, T., Yano, S., Kai, Y., Tsuiki, H., Yoshinaga, Y., Matsumoto, J., Maeda, T., Hamada, J.-I., Yamamoto, H., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.06.096 · Cited by 37 · see citing works
Long-Term Potentiation in Isolated Dendritic Spines
Corera, A. T., Doucet, G., & Fon, E. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006021 · Cited by 28 · see citing works
ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke
Gladbach, A., van Eersel, J., Bi, M., Ke, Y. D., & Ittner, L. M. (2013) · Journal of Neural Transmission · doi:10.1007/s00702-013-1138-2 · Cited by 28 · see citing works
Self-citation
Neuroprotective effects of LBP on brain ischemic reperfusion neurodegeneration.
Wang, H.-B., Li, Y., Hao, Y.-J., Wang, T.-F., Lei, Z., Wu, Y., Zhao, Q.-P., Ang, H. R., Ma, L. W., Liu, J., et al. (2013) · PubMed · Cited by 27 · see citing works
Comparison of Surgical Methods of Transient Middle Cerebral Artery Occlusion between Rats and Mice
Lee, S., Hong, Y., Sookyoung, P. A. R. K., Lee, S., Chang, K., & Hong, Y. (2014) · Journal of Veterinary Medical Science · doi:10.1292/jvms.14-0258 · Cited by 26 · see citing works
Molecular and behavioral changes associated with adult hippocampus-specific SynGAP1 knockoutPreprint
Muhia, M., Willadt, S., Yee, B. K., Feldon, J., Paterna, J., Schwendener, S., Vogt, K. E., Kennedy, M. B., & Knuesel, I. (2012) · Learning & Memory · doi:10.1101/lm.026351.112 · Cited by 25 · see citing works
Transient Cerebral Ischemia Increases Tyrosine Phosphorylation of the Synaptic RAS-GTPase Activating Protein, SynGAP
Pei, L., Teves, R. L., Wallace, M. C., & Gurd, J. W. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200108000-00008 · Cited by 23 · see citing works
Emerging neuroprotective drugs for the treatment of acute ischaemic stroke
Schmidt, A., Minnerup, J., & Kleinschnitz, C. (2013) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2013.790363 · Cited by 16 · see citing works
Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice.
Muhia, M., Feldon, J., Knuesel, I., & Yee, B. K. (2009) · Behavioral Neuroscience · doi:10.1037/a0017118 · Cited by 16 · see citing works
PSD-95 promotes CaMKII-catalyzed serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP after transient brain ischemia in rat hippocampus
Song, B., Yan, X., & Zhang, G. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.032 · Cited by 12 · see citing works

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Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics
Kent, S. A., Spires-Jones, T. L., & Durrant, C. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02196-w · Cited by 446 · see citing works
Dendritic Tau in Alzheimer’s Disease
Ittner, A., & Ittner, L. M. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.003 · Cited by 278 · see citing works
Self-citation
Cell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury
Zhang, Q., Jia, M., Wang, Y., Wang, Q., & Wu, J. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03697-8 · Cited by 295 · see citing works
Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · see citing works
The pathological role of ferroptosis in ischemia/reperfusion-related injury
Yan, H.-F., Tuo, Q., Yin, Q., & Lei, P. (2020) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2020.042 · Cited by 247 · see citing works
Tau Proteins and Tauopathies in Alzheimer’s Disease
Chong, F. P., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0574-1 · Cited by 248 · see citing works
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
Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke
Shen, Z., Xiang, M., Chen, C., Ding, F., Wang, Y., Shang, C., Xin, L., Zhang, Y., & Cui, X. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113125 · Cited by 236 · 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
Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP
Wu, F., Han, B., Wu, S., Yang, L., Leng, S., Li, M., Liao, J., Wang, G., Ye, Q., Zhang, Y., et al. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0299-19.2019 · Cited by 207 · see citing works
It’s all about tau
Tapia‐Rojas, C., Cabezas-Opazo, F., Deaton, C. A., Vergara, E. H., Johnson, G. V. W., & Quintanilla, R. A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.005 · Cited by 195 · see citing works
Understanding the Amyloid Hypothesis in Alzheimer’s Disease
Paroni, G., Bisceglia, P., & Seripa, D. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180802 · Cited by 186 · see citing works
From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation
Goulay, R., Romo, L. M., Hol, E. M., & Dijkhuizen, R. M. (2019) · Translational Stroke Research · doi:10.1007/s12975-019-00755-2 · Cited by 142 · see citing works
Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis
Penke, B., Szűcs, M., & Bogár, F. (2020) · Molecules · doi:10.3390/molecules25071659 · Cited by 115 · see citing works
Iron homeostasis imbalance and ferroptosis in brain diseases
Long, H.-N., Zhu, W.-S., Wei, L.-M., & Zhao, J.-G. (2023) · MedComm · doi:10.1002/mco2.298 · Cited by 108 · see citing works
Tau Reduction Prevents Key Features of Autism in Mouse Models
Tai, C., Chang, C.-W., Yu, G.-Q., Lopez, I., Yu, X., Wang, X., Guo, W., & Mucke, L. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.038 · Cited by 96 · see citing works
Drug delivery of memantine with carbon dots for Alzheimer’s disease: blood–brain barrier penetration and inhibition of tau aggregation
Zhang, W., Kandel, N., Zhou, Y., Smith, N. S., Ferreira, B. C. L. B., Perez, M., Claure, M. L., Mintz, K. J., Wang, C., & Leblanc, R. M. (2022) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2022.02.124 · Cited by 94 · see citing works
Much More Than a Cytoskeletal Protein: Physiological and Pathological Functions of the Non-microtubule Binding Region of Tau
Brandt, R., Trushina, N. I., & Bakota, L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590059 · Cited by 88 · see citing works
Species-conserved SYNGAP1 phenotypes associated with neurodevelopmental disorders
Kılınç, M., Creson, T. K., Rojas, C., Aceti, M., Ellegood, J., Vaissière, T., Lerch, J. P., & Rumbaugh, G. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.03.008 · Cited by 81 · see citing works
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease
Kim, N., Chen, D., Zhou, X. Z., & Lee, T. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133131 · Cited by 87 · see citing works
Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony
Chang, C.-W., Evans, M. D., Yu, X., Yu, G.-Q., & Mucke, L. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109855 · Cited by 81 · see citing works
Schisandra chinensis Fructus and Its Active Ingredients as Promising Resources for the Treatment of Neurological Diseases
Zhang, M., Xu, L., & Yang, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071970 · Cited by 77 · see citing works
Mitochondrial ferritin alleviates apoptosis by enhancing mitochondrial bioenergetics and stimulating glucose metabolism in cerebral ischemia reperfusion
Wang, P., Cui, Y., Liu, Y., Li, Z., Bai, H., Zhao, Y., & Chang, Y. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102475 · Cited by 77 · see citing works
Tau Protein Dysfunction after Brain Ischemia
Pluta, R. M., Ułamek-Kozioł, M., Januszewski, S., & Czuczwar, S. J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180772 · Cited by 73 · see citing works
Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway
Shi, Y., Zhang, X., Ying, P.-J., Wu, Z., Lin, L., Chen, W., Zheng, G., & Zhu, W. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.639898 · Cited by 73 · see citing works
Tau-induced pathology in epilepsy and dementia: notions from patients and animal models.
Sánchez, M., García-Cabrero, A., Sánchez-Elexpuru, G., Burgos, D., & Serratosa, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041092 · Cited by 68 · see citing works
Tau Phosphorylation and Aggregation in the Developing Human Brain
Hefti, M. M., Kim, S., Bell, A. J., Betters, R. K., Fiock, K. L., Iida, M. A., Smalley, M. E., Farrell, K. W., Fowkes, M. E., & Crary, J. F. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz073 · Cited by 63 · see citing works
Remodeling brain pathological microenvironment to lessen cerebral ischemia injury by multifunctional injectable hydrogels
Zhang, W., Liu, Y., Wang, Z., He, S., Liu, W., Wu, Y., Yang, L., Hu, C., & Wang, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.03.050 · Cited by 59 · see citing works
Neurodegenerative pathways as targets for acquired epilepsy therapy development
Casillas-Espinosa, P. M., Ali, I. Y., & O'Brien, T. J. (2020) · Epilepsia Open · doi:10.1002/epi4.12386 · Cited by 58 · see citing works
Expression of the Tau Protein and Amyloid Protein Precursor Processing Genes in the CA3 Area of the Hippocampus in the Ischemic Model of Alzheimer’s Disease in the Rat
Pluta, R. M., Ułamek-Kozioł, M., Kocki, J., Bogucki, J., Januszewski, S., Bogucka‐Kocka, A., & Czuczwar, S. J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01799-z · Cited by 58 · see citing works
Antipsychotic use in dementia: the relationship between neuropsychiatric symptom profiles and adverse outcomes
Mueller, C., John, C., Perera, G., Aarsland, D., Ballard, C. G., & Stewart, R. J. (2020) · European Journal of Epidemiology · doi:10.1007/s10654-020-00643-2 · Cited by 56 · see citing works
Blood tau‐PT217 contributes to the anesthesia/surgery‐induced delirium‐like behavior in aged mice
Lu, J., Liang, F., Bai, P., Liu, C., Xu, M., Sun, Z., Tian, W., Dong, Y., Zhang, Y., Quan, Q., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13118 · Cited by 51 · see citing works
Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond
Webber, E. K., Fivaz, M., Stutzmann, G. E., & Griffioen, G. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13065 · Cited by 50 · see citing works
Elevated Cerebrospinal Fluid Tau Protein Concentrations on Admission Are Associated With Long-term Neurologic and Cognitive Impairment in Ugandan Children With Cerebral Malaria
Datta, D., Conroy, A. L., Castelluccio, P., Ssenkusu, J. M., Park, G. S., Opoka, R. O., Bangirana, P., Idro, R., Saykin, A. J., & John, C. C. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz325 · Cited by 49 · see citing works
The Role of Amyloid-Beta and Tau in the Early Pathogenesis of Alzheimer’s Disease
Yin, X., Qiu, Y., Zhao, C., Zhou, Z., Bao, J., & Qian, W. (2021) · Medical Science Monitor · doi:10.12659/msm.933084 · Cited by 48 · see citing works
Galangin inhibited ferroptosis through activation of the PI3K / AKT pathway in vitro and in vivo
Chen, K., Xue, R., Geng, Y., & Zhang, S. (2022) · The FASEB Journal · doi:10.1096/fj.202200935r · Cited by 46 · see citing works
Tau is required for the function of extrasynaptic NMDA receptors
Pallas‐Bazarra, N., Draffin, J. E., Cuadros, R., Esteban, J. A., & Ávila, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-45547-8 · Cited by 46 · see citing works
Proteomic and Genomic Changes in Tau Protein, Which Are Associated with Alzheimer’s Disease after Ischemia-Reperfusion Brain Injury
Ułamek-Kozioł, M., Czuczwar, S. J., Januszewski, S., & Pluta, R. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030892 · Cited by 46 · see citing works
Fyn-tau Ablation Modifies PTZ-Induced Seizures and Post-seizure Hallmarks of Early Epileptogenesis
Putra, M. R. E., Puttachary, S., Liu, G., Lee, G. S., & Thippeswamy, T. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592374 · Cited by 47 · see citing works
Synergic Neuroprotection Between Ligusticum Chuanxiong Hort and Borneol Against Ischemic Stroke by Neurogenesis via Modulating Reactive Astrogliosis and Maintaining the Blood–Brain Barrier
Yu, B., Yao, Y., Zhang, X., Ruan, M., Zhang, Z., Xu, L., Liang, T., & Lu, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.666790 · Cited by 42 · see citing works
Tau in Oligodendrocytes Takes Neurons in Sickness and in Health
LoPresti, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082408 · Cited by 44 · see citing works
Tau as a potential therapeutic target for ischemic stroke
Chen, X., & Jiang, H. (2019) · Aging · doi:10.18632/aging.102547 · Cited by 44 · see citing works
miR-221 Exerts Neuroprotective Effects in Ischemic Stroke by Inhibiting the Proinflammatory Response
Shan, Y., Hu, J., Lv, H., Cui, X., & Di, W. (2021) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2020.105489 · Cited by 36 · see citing works
Generation of a New Tau Knockout (tau Δex1 ) Line Using CRISPR/Cas9 Genome Editing in Mice
Tan, D. C. S., Yao, S., Ittner, A., Bertz, J., Ke, Y. D., Ittner, L. M., & Delerue, F. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-171058 · Cited by 45 · see citing works
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The need to incorporate aged animals into the preclinical modeling of neurological conditions
Sun, M., McDonald, S. J., Brady, R. D., Collins‐Praino, L. E., Yamakawa, G. R., Monif, M., O'Brien, T. J., CLOUD, G. C., Sobey, C. G., Mychasiuk, R., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.027 · Cited by 43 · see citing works
Natural Compounds for SIRT1‐Mediated Oxidative Stress and Neuroinflammation in Stroke: A Potential Therapeutic Target in the Future
Fang, C., Xu, H., Yuan, L., Zhu, Z., Wang, X., Liu, Y., Zhang, A., Shao, A., & Lou, M. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1949718 · Cited by 43 · see citing works
Neuronal levels and sequence of tau modulate the power of brain rhythms
Das, M. M., Maeda, S., Hu, B., Yu, G.-Q., Guo, W., Lopez, I., Yu, X., Tai, C., Wang, X., & Mucke, L. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.020 · Cited by 41 · see citing works
NO-releasing double-crosslinked responsive hydrogels accelerate the treatment and repair of ischemic stroke
Guo, W. P., Hu, C., Wang, Y., Zhang, W., Zhang, S., Peng, J., Wang, Y., & Wu, J. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.01.005 · Cited by 39 · see citing works
Treatment with Atorvastatin During Vascular Remodeling Promotes Pericyte-Mediated Blood-Brain Barrier Maturation Following Ischemic Stroke
Yang, Y., Yang, L. Y., Salayandia, V. M., Thompson, J. F., Torbey, M., & Yang, Y. R. (2021) · Translational Stroke Research · doi:10.1007/s12975-020-00883-0 · Cited by 39 · see citing works
Loss of LAMP5 interneurons drives neuronal network dysfunction in Alzheimer’s disease
Deng, Y., Bi, M., Delerue, F., Forrest, S. L., Chan, G., van der Hoven, J., van Hummel, A., Feiten, A., Lee, S., Martínez-Valbuena, I., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02457-w · Cited by 39 · see citing works
Self-citation
Tau target identification reveals NSF‐dependent effects on AMPA receptor trafficking and memory formation
Prikas, E., Parić, E., Asih, P. R., Stefanoska, K., Stefen, H., Fath, T., Poljak, A., & Ittner, A. (2022) · The EMBO Journal · doi:10.15252/embj.2021110242 · Cited by 39 · see citing works
Self-citation
Shared genes between Alzheimer’s disease and ischemic stroke
Wei, C., Cui, P., Li, H., Lang, W., Liu, G., & Ma, X. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13117 · Cited by 37 · see citing works
Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity
Ippati, S., Deng, Y., van der Hoven, J., Heu, C., van Hummel, A., Chua, S. W., Parić, E., Chan, G., Feiten, A., Fath, T., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011876118 · Cited by 39 · see citing works
Self-citation
Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Possible Therapeutic Role of Curcumin
Pluta, R. M., Furmaga-Jabłońska, W., Januszewski, S., & Czuczwar, S. J. (2022) · Nutrients · doi:10.3390/nu14020248 · Cited by 38 · see citing works
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration
Gil, R. S., Pascovici, D., Venturato, J., Brown-Wright, H., Mehta, P. M., Martin, L. M. S., Wu, J. X., Luan, W., Chui, Y. K., Bademosi, A. T., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45646-9 · Cited by 37 · see citing works
Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation
Hayden, E. Y., Putman, J. N., Nuñez, S., Shin, W. S., Oberoi, M. R., Charreton, M., Dutta, S., Li, Z., Komuro, Y., Joy, M. T., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0783-6 · Cited by 37 · see citing works
Dendritic/Post-synaptic Tau and Early Pathology of Alzheimer’s Disease
Yin, X., Zhao, C., Qiu, Y., Zhou, Z., Bao, J., & Qian, W. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.671779 · Cited by 39 · see citing works
Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia
Pluta, R. M., Ułamek-Kozioł, M., Januszewski, S., & Czuczwar, S. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134599 · Cited by 37 · see citing works
Identification of Circular RNA hsa_circ_0001599 as a Novel Biomarker for Large-Artery Atherosclerotic Stroke
Li, S., Hu, W., Deng, F., Chen, S., Zhu, P., Wang, M., Chen, X., Wang, Y., Hu, X., Zhao, B., et al. (2021) · DNA and Cell Biology · doi:10.1089/dna.2020.5662 · Cited by 35 · see citing works
Interactions Between Ferroptosis and Oxidative Stress in Ischemic Stroke
Liu, D., Yang, S., & Yu, S. (2024) · Antioxidants · doi:10.3390/antiox13111329 · Cited by 36 · see citing works
Waking the sleeping dragon: gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps
Capraro, A., O’Meally, D., Waters, S. A., Patel, H. R., Georges, A., & Waters, P. D. (2019) · BMC Genomics · doi:10.1186/s12864-019-5750-x · Cited by 34 · see citing works
Reduction of advanced tau-mediated memory deficits by the MAP kinase p38γ
Ittner, A., Asih, P. R., Tan, A. R. P., Prikas, E., Bertz, J., Stefanoska, K., Lin, Y., Volkerling, A. M., Ke, Y. D., Delerue, F., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02191-1 · Cited by 33 · see citing works
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A natural diarylheptanoid protects cortical neurons against oxygen–glucose deprivation-induced autophagy and apoptosis
Shi, Q., Zhang, Q., Peng, Y., Zhang, X., Wang, Y., & Shi, L. (2019) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13096 · Cited by 32 · see citing works
Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects
Xu, A., Zhang, H., Zhang, Y., Wu, J., & Huang, Z. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.026 · Cited by 36 · see citing works
Participation of Amyloid and Tau Protein in Post-Ischemic Neurodegeneration of the Hippocampus of a Nature Identical to Alzheimer's Disease
Pluta, R. M., Ouyang, L., Januszewski, S., Li, Y., & Czuczwar, S. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052460 · Cited by 31 · see citing works
Blood-brain barrier dysfunction in ischemic stroke and diabetes: the underlying link, mechanisms and future possible therapeutic targets
Wicha, P., Das, S., & Mahakkanukrauh, P. (2021) · Anatomy & Cell Biology · doi:10.5115/acb.20.290 · Cited by 30 · see citing works
Secondary neurodegeneration following Stroke: what can blood biomarkers tell us?
Brunelli, S., Giannella, E., Bizzaglia, M., Angelis, D. D., & Sancesario, G. M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1198216 · Cited by 30 · see citing works
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Behl, T., Kaur, I., Sehgal, A., Khandige, P. S., Imran, M., Gulati, M., Anwer, M. K., Elossaily, G. M., Ali, N., Wal, P., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102388 · Cited by 29 · see citing works
Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat
Amini-Khoei, H., Saghaei, E., Mobini, G. R., Sabzevary‐Ghahfarokhi, M., Ahmadi, R., Bagheri, N., & Mokhtari, T. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.101942 · Cited by 29 · see citing works
Shared pathophysiology: Understanding stroke and Alzheimer’s disease
Sriram, S., Mehkri, Y., Quintin, S. S., & Lucke-Wold, B. P. (2022) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2022.107306 · Cited by 29 · see citing works
Post-Ischemic Neurodegeneration of the Hippocampus Resembling Alzheimer’s Disease Proteinopathy
Pluta, R. M., Januszewski, S., & Czuczwar, S. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010306 · Cited by 30 · see citing works
Friend or foe: role of pathological tau in neuronal death
Wu, M., Chen, Z., Jiang, M. H., Bao, B., Li, D., Yin, X., Wang, X., Liu, D., & Zhu, L. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02024-z · Cited by 28 · see citing works
Onset of hippocampal network aberration and memory deficits in P301S tau mice are associated with an early gene signature
Przybyla, M., van Eersel, J., van Hummel, A., van der Hoven, J., Sabale, M., Harasta, A. E., Müller, J., Gajwani, M., Prikas, E., Mueller, T., et al. (2020) · Brain · doi:10.1093/brain/awaa133 · Cited by 27 · see citing works
Self-citation
The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type
Pluta, R. M., Czuczwar, S. J., Januszewski, S., & Jabłoński, M. (2021) · Cells · doi:10.3390/cells10092213 · Cited by 24 · see citing works
Multi-Omics Profiling Identifies Microglial Annexin A2 as a Key Mediator of NF-κB Pro-inflammatory Signaling in Ischemic Reperfusion Injury
Tian, X., Yang, W., Jiang, W., Zhang, Z., Liu, J., & Tu, H. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100723 · Cited by 25 · see citing works
Overexpression of Slit2 decreases neuronal excitotoxicity, accelerates glymphatic clearance, and improves cognition in a multiple microinfarcts model
He, X., Li, G., Li, L., Li, M., Liang, F., Chen, X., & Hu, X. (2020) · Molecular Brain · doi:10.1186/s13041-020-00659-5 · Cited by 25 · see citing works
Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications
Shahpasand‐Kroner, H., Siddique, I. A., Malik, R., Linares, G. R., Ivanova, M. I., Ichida, J. K., Weil, T., Münch, J., Sánchez‐García, E., Klärner, F., et al. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000654 · Cited by 25 · see citing works
Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors
Kaneko, Y., Tuazon, J. P., Ji, X., & Borlongan, C. V. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495722 · Cited by 25 · see citing works
Diagnosis of cerebral malaria: Tools to reduce Plasmodium falciparum associated mortality
Muppidi, P., Wright, E., Wassmer, S. C., & Gupta, H. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1090013 · Cited by 23 · see citing works
Shared Genomic and Proteomic Contribution of Amyloid and Tau Protein Characteristic of Alzheimer’s Disease to Brain Ischemia
Pluta, R. M., Ułamek-Kozioł, M., Januszewski, S., & Czuczwar, S. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093186 · Cited by 22 · see citing works
Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn‐independent effect of tau on calcium
Liu, G., Thangavel, R., Rysted, J., Kim, Y., Francis, M. B., Adams, E., Lin, Z., Taugher, R. J., Wemmie, J. A., Usachev, Y. M., et al. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24517 · Cited by 22 · see citing works
Targeting 14-3-3θ-mediated TDP-43 pathology in amyotrophic lateral sclerosis and frontotemporal dementia mice
Ke, Y. D., van Hummel, A., Au, C. G., Chan, G., Lee, W. S., van der Hoven, J., Przybyla, M., Deng, Y., Sabale, M., Morey, N., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.01.022 · Cited by 21 · see citing works
Self-citation
Dexmedetomidine inhibits apoptosis of astrocytes induced by oxygen-glucose deprivation via targeting JAK/STAT3 signal pathway
Feng, P., Zhang, A., Su, M., Cai, H., Wang, X., & Zhang, Y. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147141 · Cited by 21 · see citing works
ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ
Rayner, S. L., Cheng, F., Hogan, A. L., Grima, N., Yang, S., Ke, Y. D., Au, C. G., Morsch, M., Luca, A. D., Davidson, J. M., et al. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab073 · Cited by 21 · see citing works
Self-citation
Biomarkers of mature neuronal differentiation and related diseases
Yuan, X., Li, W., Qi, Y., Ou, Y., Long, Q., & Zhang, P. (2024) · Future Science OA · doi:10.1080/20565623.2024.2410146 · Cited by 20 · see citing works
Tau-Induced Elevation of the Activity-Regulated Cytoskeleton Associated Protein Arc1 Causally Mediates Neurodegeneration in the Adult Drosophila Brain
Schulz, L., Ramirez, P., Lemieux, A., Gonzalez, E. M., Thomson, T., & Frost, B. E. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.04.017 · Cited by 20 · see citing works
The Two-Pore Domain Potassium Channel TREK-1 Promotes Blood–Brain Barrier Breakdown and Exacerbates Neuronal Death After Focal Cerebral Ischemia in Mice
Zheng, X., Yang, J., Zhu, Z., Fang, Y., Tian, Y., Xie, M., Wang, W., & Liu, Y. (2022) · Molecular Neurobiology · doi:10.1007/s12035-021-02702-5 · Cited by 19 · see citing works
Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death
Hoque, A., Williamson, N. A., Ameen, S. S., Ciccotosto, G. D., Hossain, M. I., Oakhill, J. S., Ng, D. C. H., Ang, C., & Cheng, H. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1445-0 · Cited by 19 · see citing works
Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats
Li, L.-L., Liu, Y., Sun, C., Yan, Y., Tang, Z., Sun, J., Li, L., Song, Z., Wang, D., Li, X.-H., et al. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113014 · Cited by 19 · see citing works
Protein Aggregation in the Pathogenesis of Ischemic Stroke
Wu, S., & Du, L. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00899-y · Cited by 18 · see citing works
An Introduction to Ultrasensitive Assays for Plasma Tau Detection
Ding, X., Tuo, Q., & Lei, P. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201499 · Cited by 19 · see citing works
Accelerated Molecular Transportation in the Brain Extracellular Space with 755-nm Light Attenuates Post-Stroke Cognitive Impairment in Rats
Yang, L., Gao, Y., Lopes, L. S., Lian, J., Fu, W., Tan, H., Yang, S., Xie, Z., Huang, Y., Zhang, J., et al. (2025) · Cyborg and Bionic Systems · doi:10.34133/cbsystems.0262 · Cited by 18 · see citing works
Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke
Au, N. P. B., Wu, T., Kumar, G., Jin, Y., Li, Y. Y. T., Chan, S. L., Lai, J. H. C., Chan, K. W. Y., Yu, K. N., Wang, X., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.09.015 · Cited by 20 · see citing works
Stroke and Alzheimer’s Disease: A Mendelian Randomization Study
Wang, T., Ni, Q., Wang, K., Han, Z., & Sun, B. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00581 · Cited by 18 · see citing works
Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy
Putra, M. R. E., Rao, N. S., Gardner, C., Liu, G., Trommater, J., Bunney, M., Gage, M., Bassuk, A. G., Hefti, M. M., Lee, G. S., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae327 · Cited by 17 · see citing works
Unraveling the dual role of bilirubin in neurological Diseases: A Comprehensive exploration of its neuroprotective and neurotoxic effects
Kaur, A., Rohit, & Aran, K. R. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149472 · Cited by 17 · see citing works
RETRACTED: Sanhua Decoction, a Classic Herbal Prescription, Exerts Neuroprotection Through Regulating Phosphorylated Tau Level and Promoting Adult Endogenous Neurogenesis After Cerebral Ischemia/Reperfusion Injury
Fu, D.-L., Li, J.-H., Shi, Y., Zhang, X.-L., Lin, Y., & Zheng, G. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00057 · Cited by 17 · see citing works
Retracted
The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity
Cisternas, P., Taylor, X., Martínez, P., Maldonado, O., Jury, N., & Lasagna‐Reeves, C. A. (2022) · Brain Communications · doi:10.1093/braincomms/fcac235 · Cited by 14 · see citing works
Tau and GSK-3β are Critical Contributors to α-Synuclein-Mediated Post-Stroke Brain Damage
Mehta, S. L., Kim, T., Chelluboina, B., & Vemuganti, R. (2022) · NeuroMolecular Medicine · doi:10.1007/s12017-022-08731-0 · Cited by 16 · see citing works

The role of tau in excitotoxicity
Gladbach, P. A. W. (2013) · UPT. Syiah Kuala University Library (Syiah Kuala University)
Genetic Factors in Excitotoxicity and Stroke
Bi, M. (2022) · UNSWorks (University of New South Wales, Sydney, Australia) · doi:10.26190/unsworks/3429
Self-citation
Tau is required for the function of extrasynaptic NMDA receptors
Pallas‐Bazarra, N., Draffin, J. E., Cuadros, R., Esteban, J. A., & Ávila, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-45547-8 · Cited by 46 · see citing works
Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture
Miyamoto, T., Stein, L. R., Thomas, R., Djukic, B., Taneja, P., Knox, J. A., Vossel, K. A., & Mucke, L. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0176-x · Cited by 100 · see citing works
Mechanisms of tau and Aβ-induced excitotoxicity
Pallo, S. P., DiMaio, J., Cook, A., Nilsson, B., & Johnson, G. V. W. (2016) · Brain Research · doi:10.1016/j.brainres.2015.12.048 · Cited by 46 · see citing works

Authors: Bi, M., Gladbach, A., van Eersel, J., Ittner, A., Przybyla, M., van Hummel, A., Chua, S. W., van der Hoven, J., Lee, W. S., Müller, J., Parmar, J., Jonquieres, G. V., Stefen, H., Guccione, E., Fath, T., Housley, G. D., Klugmann, M., Ke, Y. D., & Ittner, L. M.
Affiliations: UNSW Sydney (AU)
Agency for Science, Technology and Research (SG)
Corresponding author: Ittner, Lars M.
ORCID: Bi, Mian
Ittner, Arne
Przybyla, Magdalena
Müller, Julius
Parmar, Jasneet
Stefen, Holly
Guccione, Ernesto
Fath, Thomas
Housley, Gary D.
Klugmann, Matthias
Ke, Yazi D.
Ittner, Lars M.
Venue: Nature Communications
Publisher: Springer Science and Business Media LLC
Published: 2017-09-07
Volume: 8
Issue: 1
Pages: 473-473
ISSN: 2041-1723 (ISSN-L)
DOI: 10.1038/s41467-017-00618-0
PMC: PMC5589746
OpenAlex: W2751298713
Cited by: 167
References: 89
Citations by year: 2026: 10 · 2025: 14 · 2024: 20 · 2023: 13 · 2022: 22 · 2021: 25 · 2020: 27 · 2019: 22 · 2018: 13 · 2017: 1
FWCI: 8.43
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Nature Communications (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
National University of Singapore (submittedVersion, cc-by)
RePEc: Research Papers in Economics (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: University of New South Wales
Medical Research Council
Australian Research Council
National Health and Medical Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: tau protein, excitotoxicity, stroke, SYNGAP1, Ras/ERK signaling, glutamate receptors, middle cerebral artery occlusion, neuroprotection
MeSH terms: Animals, Brain Injuries, Cells, Cultured, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Neurons, Synaptosomes, Signal Transduction, tau Proteins, Mice, Knockout, Infarction, Middle Cerebral Artery, Stroke, ras GTPase-Activating Proteins, Gene Expression Profiling

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Tau exacerbates excitotoxic brain damage in an animal model of stroke

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