Nuclear Tau, a Key Player in Neuronal DNA Protection
Open accessAbstract
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the overexpression of human Tau targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response.
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Intranuclear tau is thought to bind to chromatin and stabilize it in response to cellular stressors such as heat.
“In particular, intranuclear tau is thought to bind to chromatin and stabilize it in response to cellular stressors such heat [149].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [149]
Nuclear tau prevents DNA damage by oxidative stress.
“prevents DNA damage by oxidative stress 94, 106”
From Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome (2016) · cites this paper as [94]
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“Nuclear tau induces DNA conformational changes in neural cells (81), protects DNA from denaturation in vitro (51, 52), prevents DNA damage by oxidative stress (94, 106), and confers stability to DNA (15, 92).”
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BackgroundMethodEctosomes: A New Mechanism for Non-Exosomal Secretion of Tau Protein
Dujardin, S., Bégard, S., Caillierez, R., Lachaud, C., Delattre, L., Carrier, S., Loyens, A., Galas, M., Bousset, L., Melki, R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100760 · Cited by 219 · see citing works
“Tau is not only associated with microtubules but also localises in other sub-cellular compartments, such as the nucleus [9] and plasma membrane [10,11], which suggests that this protein has yet unknown physiological functions.”
BackgroundSelf-citationTau 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
“Tau can directly bind DNA [88] and RNA [89] and protects them from oxidative damage [90,91] which helps to maintain DNA and RNA integrity [92].”
BackgroundAtypical, non-standard functions of the microtubule associated Tau protein
Sotiropoulos, I., Galas, M., Silva, J. M., Skoulakis, E. M. C., Wegmann, S., Maina, M. B., Blum, D. L., Sayas, C. L., Mandelkow, E., Mandelkow�, E., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0489-6 · Cited by 211 · see citing works
“In support of several articles describing a nuclear role for Tau in RNA and DNA protection [50, 75, 76], recent findings from Marie Galas and Eliette Bonnefoy’s teams suggest a structural role in pericentromeric heterochromatin (PCH) architecture, which is impaired in AD brains and a regulatory function for Tau in the…”
BackgroundSelf-citationTau deletion promotes brain insulin resistance
Marciniak, E., Leboucher, A., Caron, E., Ahmed, T., Tailleux, A., Dumont, J., Issad, T., Gerhardt, E., Pagesy, P., Vileno, M., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20161731 · Cited by 205 · see citing works
“Recently, other functions have emerged, such as the ability of tau to control neuronal excitability at dendritic spines (Ittner et al., 2010) or protect nucleic acids from oxidative stress (Sultan et al., 2011; Violet et al., 2014).”
BackgroundSelf-citationTau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment
Le Freche, H., Brouillette, J., Fernandez-Gomez, F.-J., Patin, P., Caillierez, R., Zommer, N., Sergeant, N., Buée-Scherrer, V., Lebuffe, G., Blum, D., et al. (2012) · Anesthesiology · doi:10.1097/aln.0b013e31824be8c7 · Cited by 212 · see citing works
“microtubules, contributing to axonal integrity of the normal mature neuron,(24,25) but also play a role at the dendritic and nuclear levels in neurons.(26,27) Hyperphosphorylated and ab-”
BackgroundSelf-citationTapia‐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
“Moreover, neurons exposed to heat shock show increased interactions between endogenous tau and neuronal DNA, protecting DNA from damage.”
BackgroundInfluentialRegulation of human MAPT gene expression
Caillet‐Boudin, M., Buée, L., Sergeant, N., & Lefebvre, B. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0025-8 · Cited by 195 · see citing works
“Tau is involved in axonal transport (reviewed in [4, 5]), synaptic plasticity/function (reviewed in [6, 7]) and nucleic acid protection [8, 9], depending on its cellular localization (cell body/axon, cytoplasmic membrane, or nucleus).”
BackgroundSelf-citationFrom the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy
Colin, M., Dujardin, S., Schraen-Maschke, S., Meno-Tetang, G., Duyckaerts, C., Courade, J.-P., & Buée, L. (2020) · Acta Neuropathologica · doi:10.1007/s00401-019-02087-9 · Cited by 187 · see citing works
Self-citationNuclear Tau and Its Potential Role in Alzheimer’s Disease
Bukar Maina, M., Al-Hilaly, Y., & Serpell, L. (2016) · Biomolecules · doi:10.3390/biom6010009 · Cited by 161 · see citing works
“’s study [52] also showed dense nucleolar tau staining following the heat-stress, reminiscent of Hsp70 that translocates to the nucleus and the nucleolus to protect nucleoplasmic and ribosomal DNA from DNA breaks [94].”
BackgroundInfluentialLimorenko, G., & Lashuel, H. A. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00127b · Cited by 162 · see citing works
Neuroprotective Functions for the Histone Deacetylase SIRT6
Kaluski, S., Portillo, M., Besnard, A., Stein, D., Einav, M., Zhong, L., Ueberham, U., Arendt, T., Mostoslavsky, R., Sahay, A., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.008 · Cited by 163 · see citing works
“Recent findings suggest Tau has additional roles in the nuclei, where it protects the DNA from genomic instability and chromatin relaxation (Sultan et al., 2011; Violet et al., 2014; Ziv et al., 2006).”
Liu, C., & Götz, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084849 · Cited by 155 · see citing works
“Recruitment of tau to the nucleus is determined by tau-DNA binding as unbound tau does not stay in the nucleus, as shown with the DNA-binding antibiotic netropsin [35].”
TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau
Rousseaux, M. W. C., de Haro, M., Lasagna‐Reeves, C. A., Maio, A. D., Park, J., Jafar‐Nejad, P., Al‐Ramahi, I., Sharma, A., See, L., Lü, N., et al. (2016) · eLife · doi:10.7554/elife.19809 · Cited by 150 · see citing works
“Though some studies have suggested various roles for a-Syn and tau in the nucleus (Fernández-Nogales et al., 2014; Kontopoulos et al., 2006; Sultan et al., 2011), careful studies testing the kinetics and the outcome of this nuclear build-up will surely shed light on disease pathogenesis.”
BackgroundMansuroglu, Z., Benhelli-Mokrani, H., Marcato, V., Sultan, A., Violet, M., Chauderlier, A., Delattre, L., Loyens, A., Talahari, S., Bégard, S., et al. (2016) · Scientific Reports · doi:10.1038/srep33047 · Cited by 146 · see citing works
Self-citationCalderón‐Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Delgado‐Chávez, R., Mukherjee, P. S., Kulesza, R. J., Torres‐Jardón, R., Ávila-Ramírez, J., & Villarreal-Ríos, R. (2018) · Environmental Research · doi:10.1016/j.envres.2018.03.023 · Cited by 145 · see citing works
Buchholz, S., & Zempel, H. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13784 · Cited by 145 · see citing works
Formation and Propagation of Tau Oligomeric Seeds
Gerson, J. E., & Kayed, R. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00093 · Cited by 137 · see citing works
“Once relocated to the nucleus, tau appears to protect neuronal DNA from damage under cell stress (100), which may be important in AD where DNA damage has been shown to occur (101).”
BackgroundNew Insights Into Drug Discovery Targeting Tau Protein
Soeda, Y., & Takashima, A. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.590896 · Cited by 133 · see citing works
Niewiadomska, G., Niewiadomski, W., Steczkowska, M., & Gąsiorowska, A. (2021) · Life · doi:10.3390/life11010028 · Cited by 132 · see citing works
“Tau protein plays a role also in the maintenance of genomic stability [47], protection of RNA and DNA from damage induced by oxidative stress [41,42,48], and in sustenance of the dense chromatin structure [49,50].”
BackgroundLü, J., Jun-Ye, M. I. A. O., Su, T., Liu, Y., & He, R. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.04.028 · Cited by 132 · see citing works
The role of extracellular Tau in the spreading of neurofibrillary pathology
Medina, M., & Avila, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00113 · Cited by 161 · see citing works
“neurofibrillary pathology”
BackgroundCofactors are essential constituents of stable and seeding-active tau fibrils
Fichou, Y., Lin, Y., Rauch, J. N., Vigers, M., Zeng, Z., Srivastava, M., Keller, T. J., Freed, J. H., Kosik, K. S., & Han, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810058115 · Cited by 128 · see citing works
“Although tau is mostly present in axons (30), it is also found in neuronal nuclei (31) and is suspected to traffic in the extracellular matrix (32).”
BackgroundLessons 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
“Furthermore, protection of tau knockout neurons may be conferred by nuclear tau [83].”
BackgroundP53 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
“reported to cause heterochromatin relaxation while WT tau has been reported to protect DNA [35, 108].”
BackgroundGenome instability in Alzheimer disease
Hou, Y., Song, H., Croteau, D. L., Akbari, M., & Bohr, V. A. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.04.005 · Cited by 120 · see citing works
“In response to heat shock, tau accumulated in the neuronal nucleus and protected DNA from heat shock induced DNA damage (Sultan et al., 2011; Violet et al., 2014).”
BackgroundConnecting the dots between tau dysfunction and neurodegeneration
Frost, B., Götz, J., & Feany, M. B. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.005 · Cited by 124 · see citing works
“An additional neuroprotective role for tau in response to oxidative stress is based on recent evidence from cell culture experiments in which oxidative stress causes increased levels of nuclear tau, which renders DNA more resilient to heat-shock induced damage [66], potentially by a direct interaction between tau and…”
BackgroundMicroglia in Alzheimer’s Disease in the Context of Tau Pathology
Perea, J. R., Bolós, M., & Ávila, J. (2020) · Biomolecules · doi:10.3390/biom10101439 · Cited by 127 · see citing works
Tau: The Center of a Signaling Nexus in Alzheimer's Disease
Khan, S. S., & Bloom, G. S. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00031 · Cited by 121 · see citing works
Functional Implications of Glycogen Synthase Kinase‐3‐Mediated Tau Phosphorylation
Hanger, D. P., & Noble, W. J. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/352805 · Cited by 119 · see citing works
“It has been reported that the phosphorylation of tau, particularly in response to heat stress, increases the amount of tau found in neuronal nuclei [29], although this finding is somewhat controversial [30].”
BackgroundWei, H., Gao, Z., Zheng, L., Zhang, C., Liu, Z., Yang, Y., Teng, H., Hou, L., Yin, Y., & Zou, X. (2017) · Marine Drugs · doi:10.3390/md15030077 · Cited by 119 · see citing works
“These changes cause an intracellular anomaly, cytoskeleton damage, morphology changes, and apoptosis [18].”
BackgroundPropagation of Tau via Extracellular Vesicles
Pérez, M., Avila, J., & Hernández, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00698 · Cited by 118 · see citing works
Tau Isoforms: Gaining Insight into MAPT Alternative Splicing
Corsi, A., Bombieri, C., Valenti, M. T., & Romanelli, M. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315383 · Cited by 118 · see citing works
“Several findings show that Tau plays a role in multiple functions tightly linked to cancer, such as DNA protection [55,56,92], gene expression [93–95], RNA metabolism and protein synthesis [96,97] and miRNA activity [98].”
BackgroundPotential Contribution of Exosomes to the Prion-Like Propagation of Lesions in Alzheimer’s Disease
Vingtdeux, V., Sergeant, N., & Buée, L. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00229 · Cited by 116 · see citing works
“Tau is likely secreted and is also located into the nucleus following stress conditions (Sultan et al., 2011).”
BackgroundInfluentialSelf-citationSynaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01246-y · Cited by 117 · see citing works
Tau as a therapeutic target in neurodegenerative disease
Himmelstein, D. S., Ward, S., Lancia, J. K., Patterson, K. R., & Binder, L. I. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.001 · Cited by 113 · see citing works
“Although for years no real nuclear function was assigned to tau, recently it was shown to bind to the minor grove in DNA and protect DNA from heat stress-induced damage (Sultan et al., 2011).”
Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy
Kimura, T., Sharma, G., Ishiguro, K., & Hisanaga, S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00044 · Cited by 112 · see citing works
“Tau is also found in the nucleus where it exists mainly in a dephosphorylated state (Loomis et al., 1990; Greenwood and Johnson, 1995; Sultan et al., 2011).”
BackgroundPenke, B., Szűcs, M., & Bogár, F. (2020) · Molecules · doi:10.3390/molecules25071659 · Cited by 115 · see citing works
Calderón-Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Kulesza, R. J., Mukherjee, P. S., Torres-Jardón, R., Rönkkö, T., & Doty, R. L. (2018) · Environmental Research · doi:10.1016/j.envres.2018.06.027 · Cited by 110 · see citing works
Di, J., Cohen, L. S., Corbo, C. P., Phillips, G. R., Idrissi, A. E., & Alonso, A. D. C. (2016) · Scientific Reports · doi:10.1038/srep20833 · Cited by 113 · see citing works
Sex-related differences in oxidative stress and neurodegeneration
Tenkorang, M. A. A., Snyder, B., & Cunningham, R. L. (2017) · Steroids · doi:10.1016/j.steroids.2017.12.010 · Cited by 116 · see citing works
Tau biology, tauopathy, traumatic brain injury, and diagnostic challenges
Castellani, R. J., & Perry, G. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-180721 · Cited by 110 · see citing works
“Nucleolar organization and protection of genomic DNA is still another potential function [83, 84].”
BackgroundTau as a Biomarker of Neurodegeneration
Holper, S., Watson, R., & Yassi, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137307 · Cited by 114 · see citing works
The involvement of tau in nucleolar transcription and the stress response
Maina, M. B., Bailey, L. J., Wagih, S., Biasetti, L., Pollack, S. J., Quinn, J. P., Thorpe, J. R., Doherty, A. J., & Serpell, L. C. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0565-6 · Cited by 109 · see citing works
Oxidative Stress in Alzheimer’s Disease: Should We Keep Trying Antioxidant Therapies?
Ferreira, M. E. S., de Vasconcelos, A. S., Vilhena, T. D. C., da Silva, T. L., Barbosa, A. D. S., Gomes, A. R. Q., Dolabela, M. F., & Percário, S. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0157-y · Cited by 108 · see citing works
“Sultana et al. (2011) measured the rates of protein oxidation and lipid peroxidation in mitochondria isolated from lymphocytes from healthy subjects and AD patients.”
BackgroundMethylation as a key regulator of Tau aggregation and neuronal health in Alzheimer’s disease
Balmik, A. A., & Chinnathambi, S. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00732-z · Cited by 108 · see citing works
“Arginine methylation in Tau is speculated to be involved in membrane binding of Tau and its nucleo-cytoplasmic shuttling [42, 43].”
BackgroundLi, H., Liu, C.-C., Zheng, H., & Huang, T. Y. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0139-3 · Cited by 103 · see citing works
“Tau function extends beyond microtubulebinding, and includes roles in regulating synaptic function [161], protecting RNA and DNA in early stress response [162, 163], and affecting nucleocytoplasmic”
BackgroundInsights into Disease-Associated Tau Impact on Mitochondria
Szabo, L., Eckert, A., & Grimm, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176344 · Cited by 105 · see citing works
Ke, Y. D., Dramiga, J., Schütz, U., Kril, J. J., Ittner, L. M., Schröder, H., & Götz, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035678 · Cited by 104 · see citing works
“Hence, although tau itself may have nuclear functions [36], the nuclear depletion of SFPQ identified here suggests that pathological tau may cause neuronal dysfunction, at least in part, by mislocalizing proteins with nuclear functions.”
BackgroundThe 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 106 · see citing works
“It was revealed in neuronal cultures, that nuclear Tau may regulate transcriptional activity and maintain the integrity of DNA/RNA under hyperthermia, a known strong inducer of reactive oxygen species (ROS) [90].”
BackgroundHow Can Insulin Resistance Cause Alzheimer’s Disease?
Yoon, J. H., Hwang, J., Son, S. U., Choi, J., You, S.-W., Park, H., Cha, S.-Y., & Maeng, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043506 · Cited by 104 · see citing works
Axonal degeneration in tauopathies: disease relevance and underlying mechanisms
Kneynsberg, A., Combs, B., Christensen, K., Morfini, G., & Kanaan, N. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00572 · Cited by 102 · see citing works
“…regulation of AT (LaPointe et al., 2009; Kanaan et al., 2011), nuclear and nucleolar functions (Papasozomenos and Binder, 1987; Loomis et al., 1990; Sultan et al., 2011), end-binding protein regulation (RamirezRios et al., 2016), cytoskeleton-plasma membrane interactions (Brandt et al., 1995),…”
BackgroundPathological 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
Multhaup, G., Huber, O., Buée, L., & Galas, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.677211 · Cited by 101 · see citing works
“els in neuronal nuclei have been correlated with an increase of Tau-DNA complex formation (27).”
BackgroundInfluentialSelf-citationÁlvarez, G., Aldudo, J., Alonso, M., Santana, S., & Valdivieso, F. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23003 · Cited by 101 · see citing works
“Although the presence of tau in the nuclei of neurons has been reported (Brady et al., 1995; Sultan et al., 2011), the function of neuronal nuclear tau remains unclear.”
BackgroundThe interactions of p53 with tau and Aß as potential therapeutic targets for Alzheimer’s disease
Jembrek, M. J., Slade, N., Hof, P. R., & Šimić, G. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.05.001 · Cited by 100 · see citing works
“Of note, tau has additional roles in the nucleus where it protects DNA integrity and genomic stability (Sultan et al., 2011; Violet et al., 2014; Kaluski et al., 2017).”
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator
Chatterjee, S., Cassel, R., Schneider‐Anthony, A., Mérienne, K., Cosquer, B., Tzeplaeff, L., Sinha, S. H., Kumar, M., Chaturbedy, P., Eswaramoorthy, M., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708587 · Cited by 95 · see citing works
“Interestingly, Tau protein is found in the nucleus (Wei et al, 2008; Sultan et al, 2011; Qi et al, 2015), a cellular compartment where Tau levels progressively increase during aging (Gil et al, 2017).”
BackgroundSelf-citationTau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies
Zhang, X., Wang, J., Zhang, Z., & Ye, K. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00429-6 · Cited by 106 · see citing works
“Tau in the nucleus may contribute to the preservation of genomic DNA integrity [7, 10].”
BackgroundHaines, J., Herbin, O., de la Hera, B., Vidaurre, Ó., Moy, G., Sun, Q.-X., Fung, H., Albrecht, S., Alexandropoulos, K., Mccauley, D., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3953 · Cited by 64 · see citing works
Tau-mediated synaptic damage in Alzheimer’s disease
Jadhav, S., Cubinkova, V., Zimova, I., Brezováková, V., Maďari, A., Cigánková, V., & Žilka, N. (2015) · Translational Neuroscience · doi:10.1515/tnsci-2015-0023 · Cited by 95 · see citing works
“However, some recent studies indicate a wide spread distribution of tau protein in other compartments including the nucleus [76] and dendrites [37, 77].”
BackgroundJiang, J., & Jiang, H. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3424 · Cited by 93 · see citing works
“Tau proteins are members of a family of microtubule-associated proteins, which are important in the assembly of microtubules, contribute to axonal integrity in mature neurons (43,44), and perform functions at the dendritic and nuclear level in neurons (45,46).”
Amadoro, G., Corsetti, V., Atlante, A., Florenzano, F., Capsoni, S., Bussani, R., Mercanti, D., & Calissano, P. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.08.001 · Cited by 94 · see citing works
The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy
Zhang, C., Xing, A., Tan, M., Tan, L., & Yu, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9415-8 · Cited by 91 · see citing works
“protecting DNA from damage induced by heat stress [22], stabilizing and assembling microtubules, regulating axonal transport of organelles to nerve terminals, and”
BackgroundUsardi, A., Pooler, A. M., Seereeram, A., Reynolds, C. H., Derkinderen, P., Anderton, B. H., Hanger, D. P., Noble, W. J., & Williamson, R. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08218.x · Cited by 89 · see citing works
Mutant huntingtin alters Tau phosphorylation and subcellular distribution
Blum, D. L., Herrera, F., Francelle, L., Mendes, T., Basquin, M., Obriot, H., Demeyer, D., Sergeant, N., Gerhardt, E., Brouillet, E., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu421 · Cited by 87 · see citing works
“Tau is a microtubule-associated protein widely expressed in the central nervous system, playing a role in microtubule stabilization and axonal transport (4), synaptic plasticity (5) and neuronal response to stress (6).”
BackgroundSelf-citationRNA-binding proteins Musashi and tau soluble aggregates initiate nuclear dysfunction
Montalbano, M., McAllen, S., Puangmalai, N., Sengupta, U., Bhatt, N. N., Johnson, O. D., Kharas, M. G., & Kayed, R. (2020) · Nature Communications · doi:10.1038/s41467-020-18022-6 · Cited by 86 · see citing works
Qi, H., Cantrelle, F., Benhelli‐Mokrani, H., Smet‐Nocca, C., Buée, L., Lippens, G. M., Bonnefoy, E., Galas, M., & Landrieu, I. (2015) · Biochemistry · doi:10.1021/bi5014613 · Cited by 83 · see citing works
Self-citationThe Neurotoxic Role of Extracellular Tau Protein
Sebastián‐Serrano, Á., de Diego-García, L., & Dı́az-Hernández, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040998 · Cited by 81 · see citing works
“At this location, it is postulated that tau protein might play a relevant role in DNA protection [16] and in regulating the cell cycle [17].”
BackgroundNuclear Translocation Uncovers the Amyloid Peptide Aβ42 as a Regulator of Gene Transcription*
Barucker, C., Harmeier, A., Weiske, J., Fauler, B., Albring, K. F., Prokop, S., Hildebrand, P. W., Lurz, R., Heppner, F. L., Huber, O., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.564690 · Cited by 78 · see citing works
“Similarly, under conditions of stress, Tau aggregates, which are the neuropathological hallmark of several neurodegenerative diseases, were found in the nucleus of neurons (13).”
BackgroundRegulation of neuronal microtubule dynamics by tau: Implications for tauopathies
Venkatramani, A., & Panda, D. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.04.120 · Cited by 79 · see citing works
Potential mechanisms and implications for the formation of tau oligomeric strains
Gerson, J. E., Mudher, A. K., & Kayed, R. (2016) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2016.1226251 · Cited by 73 · see citing works
“While tau in its native state is commonly located in the axonal cytoskeleton, recent studies suggest that it also has a nuclear role, binding and protecting DNA and RNA under oxidative stress conditions that also lead to the formation of toxic tau oligomers (Sultan et al., 2011; Violet et al., 2014).”
- Authors
- Sultan, A., Nesslany, F., Violet, M., Bégard, S., Loyens, A., Talahari, S., Mansuroglu, Z., Marzin, D., Sergeant, N., Humez, S., Colin, M., Bonnefoy, E., Buée, L., & Galas, M.-C.
- Affiliations
- Inserm (FR)
- Institut Pasteur de Lille (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Galas, Marie-Christine
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 286
- Issue
- 6
- Pages
- 4566-4575
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3039398
- OpenAlex
- W2155048015
- Cited by
- 421
- References
- 54
- Citations by year
- 2026: 24 · 2025: 16 · 2024: 21 · 2023: 31 · 2022: 29 · 2021: 44 · 2020: 39 · 2019: 24 · 2018: 48 · 2017: 27 · 2016: 23 · 2015: 25 · 2014: 26 · 2013: 18 · 2012: 16
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (200611)
- Agence Nationale de la Recherche
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- heat stress, oxidative stress, DNA damage, neurodegeneration, Alzheimer's disease, microtubule-associated proteins, stress response
- MeSH terms
- Alzheimer Disease, Animals, Cell Nucleus, Cells, Cultured, DNA, Humans, Neurons, Phosphorylation, tau Proteins, Mice, Knockout, Heat-Shock Response, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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