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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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“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]
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“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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BackgroundSelf-citationTunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies
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Self-citationRole of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade
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“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.”
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“binding of tau to DNA may allow protection against reactive oxygen species [316, 349], and binding to RNA may contribute to ribosome stability and miRNA activity [35].”
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Hyperphosphorylation of Tau Associates With Changes in Its Function Beyond Microtubule Stability
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“Though tau has been shown to interact with nuclear DNA, hyperphosphorylation can alter this interaction with potential changes at the chromatin and transcriptional level, thereby changing its physiological role (Hua and He, 2003; Wei et al., 2008; Padmaraju et al., 2010; Sultan et al., 2011; Qi et al., 2015).”
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“Such a role is supported by previous observations that the silencing of tau expression using small hairpin RNA produced spine loss in cultured neurons (Chen et al., 2012).”
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Zempel, H., & Mandelkow�, E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.004 · Cited by 284
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Self-citationTau Proteins and Tauopathies in Alzheimer’s Disease
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“However, previous studies have shown a wider distribution of tau in other compartments including the nucleus (Sultan et al. 2011) and dendrites (Hoover et al.”
ResultAltered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome
Hernández‐Ortega, K., Garcia‐Esparcia, P., Gil, L., Lucas, J. J., & Ferrer, I. (2016) · Brain Pathology · doi:10.1111/bpa.12335 · Cited by 245
“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).”
BackgroundTau in neurodegenerative disease
Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.23 · Cited by 222
“With tau-knockout mice having been widely applied in the research, recent reports have revealed several novel functions of tau, such as maintenance of the integrity of genomic DNA (8,9), regulation of neuronal activity (10-13), neurogenesis (14,15), iron export (16) and long-term depression (LTD) (17,18).”
BackgroundNovel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration
Li, X., Kumar, Y., Zempel, H., Mandelkow, E., Biernat, J., & Mandelkow, E. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.376 · Cited by 232
“All plasmids were verified by restriction analysis and DNA sequencing.”
BackgroundMethodEctosomes: A New Mechanism for Non-Exosomal Secretion of Tau Protein
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“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
“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 221
“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
“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
“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-”
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“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 213
“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
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
“’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].”
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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 167
“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 176
“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
“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
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Buchholz, S., & Zempel, H. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13784 · Cited by 154
Formation and Propagation of Tau Oligomeric Seeds
Gerson, J. E., & Kayed, R. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00093 · Cited by 140
“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 136
Niewiadomska, G., Niewiadomski, W., Steczkowska, M., & Gąsiorowska, A. (2021) · Life · doi:10.3390/life11010028 · Cited by 138
“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
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
“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
“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 142
“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 130
“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
“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
“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 134
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
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 124
“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 120
“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
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
“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
“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 128
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 122
“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 116
“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 119
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
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 120
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 118
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
“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 121
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 120
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 111
“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 110
“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
“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 107
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
“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 111
“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 106
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
“…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 106
Multhaup, G., Huber, O., Buée, L., & Galas, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.677211 · Cited by 101
“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 108
“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 101
“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 104
“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 119
“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
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 97
“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
“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 95
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 98
“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
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
“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
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 101
Self-citationThe Neurotoxic Role of Extracellular Tau Protein
Sebastián‐Serrano, Á., de Diego-García, L., & Díaz-Hernández, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040998 · Cited by 85
“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 83
“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 84
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 78
“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).”
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
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