mTOR regulates tau phosphorylation and degradation: implications for Alzheimer's disease and other tauopathies
Open accessAbstract
Summary: Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological tau is hyperphosphorylated and aggregates to form neurofibrillary tangles. The molecular mechanisms leading to tau accumulation remain unclear and more needs to be done to elucidate them. Age is a major risk factor for all tauopathies, suggesting that molecular changes contributing to the aging process may facilitate tau accumulation and represent common mechanisms across different tauopathies. Here, we use multiple animal models and complementary genetic and pharmacological approaches to show that the mammalian target of rapamycin (mTOR) regulates tau phosphorylation and degradation. Specifically, we show that genetically increasing mTOR activity elevates endogenous mouse tau levels and phosphorylation. Complementary to it, we further demonstrate that pharmacologically reducing mTOR signaling with rapamycin ameliorates tau pathology and the associated behavioral deficits in a mouse model overexpressing mutant human tau. Mechanistically, we provide compelling evidence that the association between mTOR and tau is linked to GSK3β and autophagy function. In summary, we show that increasing mTOR signaling facilitates tau pathology, while reducing mTOR signaling ameliorates tau pathology. Given the overwhelming evidence that reducing mTOR signaling increases lifespan and healthspan, the data presented here have profound clinical implications for aging and tauopathies and provide the molecular basis for how aging may contribute to tau pathology. Additionally, these results provide preclinical data indicating that reducing mTOR signaling may be a valid therapeutic approach for tauopathies.
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Tau hyperphosphorylation resulting from seizure-associated GSK-3β upregulation may be further exacerbated by GSK-3β-mediated mTOR activation.
“tau hyperphosphorylation resulting from seizure-associated GSK-3β upregulation may be further exacerbated by GSK-3β-mediated mTOR activation (Caccamo et al., 2013; Figure 2).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Caccamo et al., 2013
The Results (page unavailable) report that increasing mTOR signaling increases tau phosphorylation through a GSK-3β-mediated mechanism. They do not show that GSK-3β activates mTOR; the proposed direction of that link is reversed. The paper also does not establish seizure-associated GSK-3β upregulation, although the Discussion mentions epilepsy as a feature of tuberous sclerosis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn seizure disorders such as tuberous sclerosis complex and Niemann-Pick type C disease characterized by autophagy dysregulation, an increase in normal tau levels may in turn contribute to both seizure activity and PTEN inhibition, creating a feedback loop of mTOR overactivation that results in further hyperphosphorylation of tau.
“In seizure disorders such as TSC and NPC that are characterized by autophagy dysregulation (Pacheco et al., 2009; Caccamo et al., 2013), increase in normal tau levels may in turn contribute to both seizure activity and PTEN inhibition, creating a feedback loop of mTOR overactivation that results in further hyperphosphorylation of tau (Figure 3).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Caccamo et al., 2013
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Experimental — accuracy not yet measuredReduced autophagy resulting from mTOR overactivation is implicated in elevated endogenous tau levels in the TSC2 mouse model of tuberous sclerosis complex.
“Furthermore, reduced autophagy resulting from mTOR overactivation is implicated in elevated endogenous tau levels in the TSC2 mouse model of TSC (Caccamo et al., 2013).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Caccamo et al., 2013
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Cites
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Self-citationRapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · 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
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120 · see citing works
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts
Mumby, D. G., Gaskin, S., Glenn, M. J., Schramek, T. E., & Lehmann, H. (2002) · Learning & Memory · doi:10.1101/lm.41302 · Cited by 714 · see citing works
Griffin, R. J., Moloney, A., Kelliher, M., Johnston, J. A., Ravid, R., Dockery, P., O'Connor, R., & O'Neill, C. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02949.x · Cited by 459 · see citing works
Chang, R. C. C., Wong, A. K. Y., Ng, H.-K., & Hugon, J. (2002) · NeuroReport · doi:10.1097/00001756-200212200-00011 · Cited by 289 · see citing works
TOR-Mediated Cell-Cycle Activation Causes Neurodegeneration in a Drosophila Tauopathy Model
Khurana, V., Lu, Y., Steinhilb, M. L., Oldham, S., Shulman, J. M., & Feany, M. B. (2006) · Current Biology · doi:10.1016/j.cub.2005.12.042 · Cited by 266 · see citing works
Flagged first, then by citations
Research works printed but not linked: 31
- An WL Cowburn RF Li L Braak H Alafuzoff I Iqbal K Iqbal IG Winblad B Pei JJ Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease The American journal of pathology 2003 163 591 607 12875979 PMC1868198
- Bertram L Tanzi RE The genetics of Alzheimer's disease Prog Mol Biol Transl Sci 2012 107 79 100 22482448
- Caccamo A Magri A Oddo S Age-dependent changes in TDP-43 levels in a mouse model of Alzheimer disease are linked to Abeta oligomers accumulation Molecular neurodegeneration 2010a 5 51 21070634 PMC2989316
- Caccamo A Majumder S Oddo S Cognitive decline typical of frontotemporal lobar degeneration in transgenic mice expressing the 25-kDa C-terminal fragment of TDP-43 The American journal of pathology 2012 180 293 302 22067910 PMC3338346
- Caccamo A Majumder S Richardson A Strong R Oddo S Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments The Journal of biological chemistry 2010b 285 13107 13120 20178983 PMC2857107
- Caccamo A Maldonado MA Bokov AF Majumder S Oddo S CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease Proceedings of the National Academy of Sciences of the United States of America 2010c 107 22687 22692 21149712 PMC3012497
- Caccamo A Maldonado MA Majumder S Medina DX Holbein W Magri A Oddo S Naturally secreted amyloid-beta increases mammalian target of rapamycin (mTOR) activity via a PRAS40-mediated mechanism The Journal of biological chemistry 2011 286 8924 8932 21266573 PMC3058958
- Cohen P Goedert M GSK3 inhibitors: development and therapeutic potential Nature reviews. Drug discovery 2004 3 479 487 15173837
- Consortium ECTS Identification and characterization of the tuberous sclerosis gene on chromosome 16 Cell 1993 75 1305 1315 8269512
- Das F Ghosh-Choudhury N Mahimainathan L Venkatesan B Feliers D Riley DJ Kasinath BS Choudhury GG Raptor-rictor axis in TGFbeta-induced protein synthesis Cellular signalling 2008 20 409 423 18068336
- Gipson TT Johnston MV Plasticity and mTOR: towards restoration of impaired synaptic plasticity in mTOR-related neurogenetic disorders Neural Plast 2012 2012 486402 22619737 PMC3350854
- Guertin DA Sabatini DM Defining the role of mTOR in cancer Cancer cell 2007 12 9 22 17613433
- Majumder S Caccamo A Medina DX Benavides AD Javors MA Kraig E Strong R Richardson A Oddo S Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1beta and enhancing NMDA signaling Aging Cell 2012 11 326 335 22212527 PMC3306461
- Majumder S Richardson A Strong R Oddo S Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits PloS one 2011 6 e25416 21980451 PMC3182203
- Medina DX Caccamo A Oddo S Methylene blue reduces abeta levels and rescues early cognitive deficit by increasing proteasome activity Brain pathology 2011 21 140 149 20731659 PMC2992595
- Meske V Albert F Ohm TG Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3-dependent phosphorylation of Tau The Journal of biological chemistry 2008 283 100 109 17971449
- Mizushima N Noda T Yoshimori T Tanaka Y Ishii T George MD Klionsky DJ Ohsumi M Ohsumi Y A protein conjugation system essential for autophagy Nature 1998 395 395 398 9759731
- Oddo S The role of mTOR signaling in Alzheimer disease Front Biosci (Schol Ed) 2012 4 941 952 22202101 PMC4111148
- Oddo S Billings L Kesslak JP Cribbs DH LaFerla FM Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome Neuron 2004 43 321 332 15294141
- Oddo S Caccamo A Cheng D Jouleh B Torp R LaFerla FM Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice Journal of neurochemistry 2007 102 1053 1063 17472708
- Oddo S Caccamo A Tseng B Cheng D Vasilevko V Cribbs DH LaFerla FM Blocking Abeta42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein: a mechanistic link between Abeta and tau pathology J Neurosci 2008 28 12163 12175 19020010 PMC6671718
- Oddo S Vasilevko V Caccamo A Kitazawa M Cribbs DH LaFerla FM Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles The Journal of biological chemistry 2006 281 39413 39423 17056594
- Onda H Lueck A Marks PW Warren HB Kwiatkowski DJ Tsc2(+/−) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background The Journal of clinical investigation 1999 104 687 695 10491404 PMC408440
- Peel AL Bredesen DE Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice Neurobiology of disease 2003 14 52 62 13678666
- Pei JJ Bjorkdahl C Zhang H Zhou X Winblad B p70 S6 kinase and tau in Alzheimer's disease J Alzheimers Dis 2008 14 385 392 18688088
- Prabowo AS Anink JJ Lammens M Nellist M van den Ouweland AM Adle-Biassette H Sarnat HB Flores-Sarnat L Crino PB Aronica E Fetal Brain Lesions in Tuberous Sclerosis Complex: TORC1 Activation and Inflammation Brain pathology 2012 PMC3518755 22805177
- Roberson ED Scearce-Levie K Palop JJ Yan F Cheng IH Wu T Gerstein H Yu GQ Mucke L Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model Science (New York, N.Y 2007 316 750 754 17478722
- Sarkar S Rubinsztein DC Huntington's disease: degradation of mutant huntingtin by autophagy Febs J 2008 275 4263 4270 18637946
- van Slegtenhorst M de Hoogt R Hermans C Nellist M Janssen B Verhoef S Lindhout D van den Ouweland A Halley D Young J Burley M Jeremiah S Woodward K Nahmias J Fox M Ekong R Osborne J Wolfe J Povey S Snell RG Cheadle JP Jones AC Tachataki M Ravine D Sampson JR Reeve MP Richardson P Wilmer F Munro C Hawkins TL Sepp T Ali JB Ward S Green AJ Yates JR Kwiatkowska J Henske EP Short MP Haines JH Jozwiak S Kwiatkowski DJ Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34 Science (New York, N.Y 1997 277 805 808 9242607
- Wang IF Guo BS Liu YC Wu CC Yang CH Tsai KJ Shen CK Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43 Proceedings of the National Academy of Sciences of the United States of America 2012 109 15024 15029 22932872 PMC3443184
- Wullschleger S Loewith R Hall MN TOR signaling in growth and metabolism Cell 2006 124 471 484 16469695
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Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003 · see citing works
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Piras, A., Collin, L., Grüninger, F., Graff, C., & Rönnbäck, A. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0292-9 · Cited by 271 · see citing works
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Denk, J., Boelmans, K., Siegismund, C., Lassner, D., Arlt, S., & Jahn, H. (2015) · PLOS ONE · doi:10.1371/journal.pone.0126423 · Cited by 236 · see citing works
Wang, C., Zhang, X., Teng, Z., Zhang, T., & Li, Y. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.06.051 · Cited by 233 · see citing works
Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases
Chu, C. T. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.07.015 · Cited by 218 · see citing works
Autophagy in Alzheimer’s disease
Zare-shahabadi, A., Masliah, E., Johnson, G. V. W., & Rezaei, N. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0076 · Cited by 204 · see citing works
Agis-Torres, A., Sollhuber, M., Fernandez, M., & Sanchez-Montero, J. M. (2014) · Current Neuropharmacology · doi:10.2174/1570159x113116660047 · Cited by 202 · see citing works
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Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D. A., & Di Domenico, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.007 · Cited by 155 · see citing works
Gourmaud, S., Shou, H., Irwin, D. J., Sansalone, K., Jacobs, L. M., Lucas, T. H., Marsh, E. D., Davis, K. A., Jensen, F. E., & Talos, D. M. (2020) · Brain · doi:10.1093/brain/awz381 · Cited by 155 · see citing works
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Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.008 · Cited by 133 · see citing works
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Barini, E., Antico, O., Zhao, Y., Asta, F., Tucci, V., Catelani, T., Marotta, R., Xu, H., & Gasparini, L. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0082-7 · Cited by 126 · see citing works
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Koren, S. A., Hamm, M. J., Meier, S. E., Weiss, B. E., Nation, G. K., Chishti, E. A., Arango, J. P., Chen, J., Zhu, H., Blalock, E. M., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01970-9 · Cited by 122 · see citing works
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114 · see citing works
Hu, Z., Chen, P.-H., Li, W., Douglas, T., Hines, J., Liu, Y., & Crews, C. M. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c11706 · Cited by 98 · see citing works
Wang, L., Bharti, Kumar, R., Pavlov, P. F., & Winblad, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112915 · Cited by 92 · see citing works
Norambuena, A., Wallrabe, H., McMahon, L., Silva, A., Swanson, E., Khan, S. S., Baerthlein, D., Kodis, E., Oddo, S., Mandell, J. W., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.08.015 · Cited by 79 · see citing works
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Norambuena, A., Wallrabe, H., Cao, R., Wang, D. B., Silva, A., Svindrych, Z., Periasamy, A., Hu, S., Tanzi, R. E., Kim, D. Y., et al. (2018) · The EMBO Journal · doi:10.15252/embj.2018100241 · Cited by 61 · see citing works
Self-citationLee, H.-K., Kwon, B., Lemere, C. A., de la Monte, S., Itamura, K., Ha, A. Y., & Querfurth, H. W. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161029 · Cited by 57 · see citing works
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Wu, J., Zhou, S.-L., Pi, L.-H., Shi, X.-J., Ma, L.-R., Chen, Z., Qu, M.-L., Li, X., Nie, S.-D., Liao, D.-F., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17257 · Cited by 50 · see citing works
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Gąssowska-Dobrowolska, M., Czapski, G. A., Cieślik, M., Zajdel, K., Frontczak-Baniewicz, M., Babiec, L., & Adamczyk, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087303 · Cited by 10 · see citing works
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- Authors
- Caccamo, A., Magrì, A., Medina, D. X., Wisely, E. V., López‐Aranda, M. F., Silva, A. J., & Oddo, S.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of California, Los Angeles (US)
- Corresponding author
- Oddo, Salvatore
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-03-24
- Volume
- 12
- Issue
- 3
- Pages
- 370-380
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3655115
- OpenAlex
- W2011134915
- Cited by
- 362
- References
- 11
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 19 · 2023: 22 · 2022: 24 · 2021: 31 · 2020: 35 · 2019: 35 · 2018: 33 · 2017: 27 · 2016: 22 · 2015: 33 · 2014: 26 · 2013: 11
- FWCI
- 21.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, other-oa)
- Funders
- Glenn Foundation for Medical Research
- National Institute on Aging (F30AG043248, R01AG037637)
- National Institute of Mental Health (R01MH084315)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- mTOR signaling, tau phosphorylation, tau degradation, tauopathy, Alzheimer's disease, frontotemporal dementia, GSK3β, autophagy, rapamycin, neurofibrillary tangles, aging, healthspan, therapeutic target
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Alzheimer Disease, Animals, Autophagy, Disease Models, Animal, Humans, Immunosuppressive Agents, Mice, Transgenic, Microtubules, Phosphorylation, Up-Regulation, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Sirolimus, Tauopathies, Tumor Suppressor Proteins, Glycogen Synthase Kinase 3, Mice, Frontotemporal Dementia, TOR Serine-Threonine Kinases
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