Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease
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BACKGROUND: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Aβ)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer's disease (AD). METHODOLOGY/PRINCIPAL FINDINGS: We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Aβ1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Aβ-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Aβ42 with mTOR. CONCLUSIONS/SIGNIFICANCE: These data support the notion that the mTOR pathway modulates Aβ-related synaptic dysfunction in AD.
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mTOR activity, which is increased by Reelin signaling, is lower in AD mice.
“mTOR activity, which is increased by Reelin signaling (92), is lower in AD mice (93).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [93]
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Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
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
Rapamycin 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
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,659 · see citing works
Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · see citing works
Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.10.007 · Cited by 1,409 · see citing works
Translational control of gene expression
Sonenberg, N., Hershey, J. W. B., & Mathews, M. B. (2000) · Medical Entomology and Zoology · Cited by 1,378 · see citing works
Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.055 · Cited by 1,377 · see citing works
The role of calcium in neuromuscular facilitation
Katz, B., & Miledi, R. (1968) · The Journal of Physiology · doi:10.1113/jphysiol.1968.sp008469 · Cited by 1,347 · see citing works
mTOR signaling: At the crossroads of plasticity, memory and disease
Hoeffer, C. A., & Klann, E. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.003 · Cited by 1,128 · see citing works
Self-citationRibosomal 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
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · 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
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Self-citationDendritic Protein Synthesis, Synaptic Plasticity, and Memory
Sutton, M. A., & Schuman, E. M. (2006) · Cell · doi:10.1016/j.cell.2006.09.014 · Cited by 894 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
Intranasal insulin improves cognition and modulates β-amyloid in early AD
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R., Breitner, J. C. S., DeGroodt, W., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000265401.62434.36 · Cited by 830 · see citing works
Takahashi, R. H., Milner, T. A., Li, F., Nam, E. E., Edgar, M. A., Yamaguchi, H., Beal, M. F., Xu, H., Greengard, P., & Gouras, G. K. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64463-x · Cited by 706 · see citing works
Self-citationβ-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity
Zheng, H., Jiang, M., Trumbauer, M. E., SIRINATHSINGHJI, D. J. S., Hopkins, R., Smith, D. W., HEAVENS, R. P., Dawson, G. R., Boyce, S., Conner, M. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90073-x · Cited by 705 · see citing works
Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease
Jacobsen, J. S., Wu, C.-C., Redwine, J. M., Comery, T. A., Arias, R., Bowlby, M., Martone, R., Morrison, J. H., Pangalos, M. N., Reinhart, P. H., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600948103 · Cited by 701 · see citing works
De Felice, F. G., Vieira, M. N. N., Bomfim, T. R., Decker, H., Velasco, P. T., Lambert, M. P., Viola, K. L., Zhao, W.-Q., Ferreira, S. T., & Klein, W. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809158106 · Cited by 657 · cited 1× · see citing works
“On one hand, Ab was shown to impair insulin-PI3K-AKT signaling [2,45–47] and insulin treatment was reported to improve cognitive function in patients with early AD [48], while on the other hand, AD transgenic mice with reduced insulin signaling were reported to be protected against cognitive decline [49].”
BackgroundYang, Q., & Guan, K. (2007) · Cell Research · doi:10.1038/cr.2007.64 · Cited by 540 · see citing works
Reduced IGF-1 signaling delays age-associated proteotoxicity in mice
Cohen, E., Paulsson, J. F., Blinder, P., Burstyn-Cohen, T., Du, D., Estepa, G., Adame, A., Pham, H. M., Holzenberger, M., Kelly, J. W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.014 · Cited by 488 · see citing works
Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
Almeida, C. G., Tampellini, D., Takahashi, R. H., Greengard, P., Lin, M. T., Snyder, E. M., & Gouras, G. K. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.008 · Cited by 397 · see citing works
Self-citationTomiyama, T., Matsuyama, S., Iso, H., Umeda, T., Takuma, H., Ohnishi, K., Ishibashi, K., Teraoka, R., Sakama, N., Yamashita, T., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5825-09.2010 · Cited by 396 · see citing works
Reiling, J. H., & Sabatini, D. M. (2006) · Oncogene · doi:10.1038/sj.onc.1209889 · Cited by 338 · see citing works
GSK3: a possible link between beta amyloid peptide and tau protein
Hernández, F., Gómez de Barreda, E., Fuster-Matanzo, A., Lucas, J. J., & Avila, J. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2009.09.011 · Cited by 327 · see citing works
Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway
Townsend, M., Mehta, T., & Selkoe, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610390200 · Cited by 318 · see citing works
An, W.-L., Cowburn, R. F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.-G., Winblad, B., & Pei, J.-J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63687-5 · Cited by 312 · see citing works
Amyloid Activates GSK-3β to Aggravate Neuronal Tauopathy in Bigenic Mice
Terwel, D., Muyllaert, D., Dewachter, I., Borghgraef, P., Croes, S., Devijver, H., & Van Leuven, F. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.070904 · Cited by 300 · see citing works
Olfactory Dysfunction Correlates with Amyloid-β Burden in an Alzheimer's Disease Mouse Model
Wesson, D. W., Levy, E., Nixon, R. A., & Wilson, D. A. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4622-09.2010 · Cited by 290 · see citing works
The Growing Role of mTOR in Neuronal Development and Plasticity
Jaworski, J., & Sheng, M. (2006) · Molecular Neurobiology · doi:10.1385/mn:34:3:205 · Cited by 268 · see citing works
The role of GSK‐3 in synaptic plasticity
Peineau, S., Bradley, C. A., Taghibiglou, C., Doherty, A., Bortolotto, Z. A., Wang, Y. T., & Collingridge, G. L. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.2 · Cited by 263 · see citing works
Banko, J. L., Hou, L., Poulin, F., Sonenberg, N., & Klann, E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5196-05.2006 · Cited by 245 · see citing works
Self-citationTsokas, P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0599-05.2005 · Cited by 242 · see citing works
Runz, H., Rietdorf, J., Tomic, I., de Bernard, M., Beyreuther, K. T., Pepperkok, R., & Hartmann, T. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01679.2002 · Cited by 242 · see citing works
Hoeffer, C. A., Tang, W., Wong, H., Santillan, A., Patterson, R. J., Martinez, L. A., Tejada-Simon, M. V., Paylor, R. E., Hamilton, S. L., & Klann, E. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.037 · Cited by 235 · see citing works
Self-citationZhu, L.-Q., Wang, S.-H., Liu, D., Yin, Y.-Y., Tian, Q., Wang, X.-C., Wang, Q., Chen, J.-G., & Wang, J.-Z. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3321-07.2007 · Cited by 234 · see citing works
Lafay‐Chebassier, C., Paccalin, M., Page, G., Barc‐Pain, S., Perault‐Pochat, M. C., Gil, R., Pradier, L., & Hugon, J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03187.x · Cited by 211 · see citing works
The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid
Lee, H., Kumar, P., Fu, Q., Rosen, K. M., & Querfurth, H. W. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0777 · Cited by 205 · see citing works
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance
Balaraman, Y., Limaye, A. R., Levey, A. I., & Srinivasan, S. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5597-y · Cited by 167 · see citing works
The Late Endosome is Essential for mTORC1 Signaling
Flinn, R. J., Yan, Y., Goswami, S., Parker, P. J., & Backer, J. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-09-0756 · Cited by 158 · see citing works
Piper, M. D. W., Selman, C., McElwee, J. J., & Partridge, L. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01906.x · Cited by 154 · see citing works
GSK-3β Is Required for Memory Reconsolidation in Adult Brain
Kimura, T., Yamashita, S., Nakao, S., Park, J.-M., Murayama, M., Mizoroki, T., Yoshiike, Y., Sahara, N., & Takashima, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003540 · Cited by 136 · see citing works
Tampellini, D., Rahman, N., Gallo, E. F., Huang, Z., Dumont, M., Capetillo-Zarate, E., Ma, T., Zheng, R., Lu, B., Nanus, D. M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2292-09.2009 · Cited by 127 · see citing works
Self-citationGobert, D., Topolnik, L., Azzi, M., Huang, L., Badeaux, F., DesGroseillers, L., Sossin, W. S., & Lacaille, J. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05470.x · Cited by 96 · see citing works
Initiation of TCR Phosphorylation and Signal Transduction
Gascoigne, N. R. J., Casas, J., Brzostek, J., & Rybakin, V. (2011) · Frontiers in Immunology · doi:10.3389/fimmu.2011.00072 · Cited by 55 · see citing works
Mind the GAP: Wnt Steps onto the mTORC1 Train
Choo, A. Y., Roux, P. P., & Blenis, J. (2006) · Cell · doi:10.1016/j.cell.2006.08.025 · Cited by 43 · see citing works
23 S6 Phosphorylation and Signal TransductionPreprint
Fumagalli, S., & Thomas, G. (2000) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969618.39.695 · Cited by 23 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
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Bomfim, T. R., Forny‐Germano, L., Sathler, L. B., Brito‐Moreira, J., Houzel, J., Decker, H., Silverman, M. A., Kazi, H., Melo, H. M., McClean, P. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57256 · Cited by 830 · see citing works
Rajmohan, R., & Reddy, P. H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160612 · Cited by 695 · see citing works
Suppression of eIF2α kinases alleviates Alzheimer's disease–related plasticity and memory deficits
Ma, T., Trinh, M. A., Wexler, A. J., Bourbon, C., Gatti, E., Pierre, P., Cavener, D. R., & Klann, E. (2013) · Nature Neuroscience · doi:10.1038/nn.3486 · Cited by 571 · see citing works
Self-citationmTOR in Brain Physiology and Pathologies
Bockaert, J., & Marin, P. (2015) · Physiological Reviews · doi:10.1152/physrev.00038.2014 · Cited by 360 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer's disease
Akhtar, A., & Sah, S. P. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104707 · Cited by 286 · see citing works
The biological pathways of Alzheimer disease: a review
Calabrò, M., Rinaldi, C., Santoro, G., & Crisafulli, C. (2020) · AIMS neuroscience · doi:10.3934/neuroscience.2021005 · Cited by 271 · see citing works
JNK3 Perpetuates Metabolic Stress Induced by Aβ Peptides
Yoon, S. O., Park, D. J., Ryu, J. C., Özer, H. G., Tep, C., Shin, Y. J., Lim, T. H., Pastorino, L., Kunwar, A. J., Walton, J. C., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.024 · Cited by 236 · see citing works
Avrahami, L., Farfara, D., Shaham-Kol, M., Vassar, R. J., Frenkel, D., & Eldar-Finkelman, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.409250 · Cited by 232 · see citing works
Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease
Burillo, J., Marqués, P., Jiménez, B., González-Blanco, C., Benito, M., & Guillén, C. (2021) · Cells · doi:10.3390/cells10051236 · Cited by 234 · see citing works
The PI3K/Akt signaling axis in Alzheimer’s disease: a valuable target to stimulate or suppress?
Razani, E., Pourbagheri‐Sigaroodi, A., Safaroghli‐Azar, A., Zoghi, A., Bavarsad, M. S., & Bashash, D. (2021) · Cell Stress and Chaperones · doi:10.1007/s12192-021-01231-3 · Cited by 229 · see citing works
mTOR: on target for novel therapeutic strategies in the nervous system
Maiese, K., Chong, Z. Z., Shang, Y., & Wang, S. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.11.001 · Cited by 226 · see citing works
Li, Q., Zhang, T., Wang, J., Zhang, Z., Zhai, Y., Yang, G.-Y., & Sun, X. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.01.032 · Cited by 209 · 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
Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders
Maiese, K. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12804 · Cited by 200 · see citing works
Ma, T., Chen, Y., Vingtdeux, V., Zhao, H., Viollet, B., Marambaud, P., & Klann, E. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1694-14.2014 · Cited by 191 · see citing works
Self-citationGlycogen synthase kinase-3 inhibitors: Rescuers of cognitive impairments
King, M. K., Pardo, M., Cheng, Y., Downey, K., Jope, R. S., & Beurel, E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.010 · Cited by 172 · see citing works
Autophagy in the presynaptic compartment in health and disease
Vijayan, V., & Verstreken, P. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201611113 · Cited by 167 · see citing works
Lahmy, V., Meunier, J., Malmström, S., Naert, G., Givalois, L., Kim, S. H., Villard, V., Vamvakides, A., & Maurice, T. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.70 · Cited by 163 · see citing works
Activation of mTOR: a culprit of Alzheimer’s disease?
Cai, Z., Zhou, Y., Xiao, M., Yan, L.-J., & He, W. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s75717 · Cited by 161 · see citing works
Mammalian Target of Rapamycin: Hitting the Bull′s‐Eye for Neurological Disorders
Chong, Z. Z., Shang, Y., Zhang, L., Wang, S., & Maiese, K. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.6.14787 · Cited by 149 · see citing works
PTEN recruitment controls synaptic and cognitive function in Alzheimer's models
Knafo, S., Sánchez‐Puelles, C., Palomer, E., Delgado, I., Draffin, J. E., Mingo, J., Wahle, T., Kaleka, K. S., Mou, L., Pereda-Pérez, I., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4225 · Cited by 147 · see citing works
Ma, T., Hoeffer, C. A., Wong, H., Massaad, C. A., Zhou, P., Iadecola, C., Murphy, M. P., Pautler, R. G., & Klann, E. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6566-10.2011 · Cited by 146 · see citing works
Self-citationD’Amelio, M., & Rossini, P. M. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.07.001 · Cited by 144 · see citing works
Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments
Bartzokis, G. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.01.015 · Cited by 142 · see citing works
Calcium channel blocking as a therapeutic strategy for Alzheimer's disease: The case for isradipine
Anekonda, T. S., & Quinn, J. F. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.08.013 · Cited by 136 · see citing works
Targeting the mTOR Signaling Network for Alzheimer’s Disease Therapy
Wang, C., Yu, J., Miao, D., Wu, Z., Tan, M., & Tan, L. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8505-8 · Cited by 133 · see citing works
Cai, Z., Zhao, B., Li, K., Zhang, L., Li, C., Quazi, S. H., & Tan, Y. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23011 · Cited by 134 · see citing works
Spines, plasticity, and cognition in Alzheimer's model mice
Spires-Jones, T., & Knafo, S. (2012) · Neural Plasticity · doi:10.1155/2012/319836 · Cited by 133 · see citing works
Amyloid β: linking synaptic plasticity failure to memory disruption in Alzheimer’s disease
Ma, T., & Klann, E. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07506.x · Cited by 131 · see citing works
Self-citationLeptin regulation of hippocampal synaptic function in health and disease
Irving, A. J., & Harvey, J. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0155 · Cited by 123 · see citing works
Moreira, N. C. D. S., Lima, J. E. B. D. F., Marchiori, M. F., Carvalho, I., & Sakamoto‐Hojo, E. T. (2022) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-210061 · Cited by 132 · see citing works
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R., & Cowart, M. (2010) · Cited by 125 · see citing works
A Critical Kinase Cascade In Neurological Disorders: Pi3K, Akt and Mtor
Chong, Z. Z., Shang, Y., Wang, S., & Maiese, K. (2012) · Future Neurology · doi:10.2217/fnl.12.72 · Cited by 119 · see citing works
Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin
Chong, Z. Z., Shang, Y. C., Wang, S., & Maiese, K. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.08.001 · Cited by 119 · see citing works
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Sala Frigerio, C., & De Strooper, B. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014015 · Cited by 116 · see citing works
Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses
Wasser, C. R., & Herz, J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.766782 · Cited by 111 · see citing works
“mTOR activity, which is increased by Reelin signaling (92), is lower in AD mice (93).”
BackgroundOxidant Stress and Signal Transduction in the Nervous System with the PI 3-K, Akt, and mTOR Cascade
Maiese, K., Chong, Z. Z., Wang, S., & Shang, Y. C. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131113830 · Cited by 109 · see citing works
Protein Homeostasis, Aging and Alzheimer’s Disease
Morawe, T., Hiebel, C., Kern, A., & Behl, C. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8246-0 · Cited by 107 · see citing works
WISP1: Clinical Insights for a Proliferative and Restorative Member of the CCN Family
Maiese, K. (2014) · Current Neurovascular Research · doi:10.2174/1567202611666140912115107 · Cited by 103 · see citing works
Ma, T., Du, X., Pick, J. E., Sui, G., Brownlee, M., & Klann, E. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2107-12.2012 · Cited by 104 · see citing works
Self-citationGlutamate receptors in preclinical research on Alzheimer's disease: Update on recent advances
Hu, N., Ondrejčák, T., & Rowan, M. J. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.04.013 · Cited by 99 · see citing works
Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
Tramutola, A., Lanzillotta, C., Barone, E., Arena, A., Zuliani, I., Mosca, L., Blarzino, C., Butterfield, D. A., Marzia Perluigi, A., & Domenico, F. D. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0133-9 · Cited by 101 · see citing works
Regulation of mTORC1 by Upstream Stimuli
Melick, C. H., & Jewell, J. L. (2020) · Genes · doi:10.3390/genes11090989 · Cited by 80 · see citing works
Targeting Synaptic Dysfunction in Alzheimer’s Disease Therapy
Nisticò, R., Pignatelli, M., Piccinin, S., Mercuri, N. B., & Collingridge, G. L. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8324-3 · Cited by 97 · see citing works
The role of mTOR signaling pathway in spinal cord injury
Kanno, H., Ozawa, H., Sekiguchi, A., Yamaya, S., Tateda, S., Yahata, K., & Itoi, E. (2012) · Cell Cycle · doi:10.4161/cc.21262 · Cited by 97 · see citing works
Lachance, V., Wang, Q., Sweet, E., Choi, I., Cai, C.-Z., Zhuang, X.-X., Zhang, Y., Jiang, J. L., Blitzer, R. D., Bozdagi-Gunal, O., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0342-4 · Cited by 96 · see citing works
Self-citationErythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia
Shang, Y., Chong, Z. Z., Wang, S., & Maiese, K. (2011) · Current Neurovascular Research · doi:10.2174/156720211798120990 · Cited by 96 · see citing works
<scp>mTOR</scp> signaling and Alzheimer's disease: What we know and where we are?
Davoody, S., Asgari Taei, A., Khodabakhsh, P., & Dargahi, L. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14463 · Cited by 96 · see citing works
Weber, J. D., & Gutmann, D. H. (2012) · Cell Cycle · doi:10.4161/cc.11.2.19022 · Cited by 92 · see citing works
Rapamycin, Autophagy, and Alzheimer's Disease.
Cai, Z., & Yan, L. (2013) · PubMed · Cited by 91 · see citing works
Erythropoietin: New Directions for the Nervous System
Maiese, K., Chong, Z. Z., Shang, Y. C., & Wang, S. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911102 · Cited by 92 · see citing works
Neurodegenerative Pathways in Alzheimer’s Disease: A Review
Ramachandran, A. K., Das, S., Joseph, A., Shenoy, G. G., Alex, A. T., & Mudgal, J. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200807130637 · Cited by 94 · see citing works
Smith, E. D., Prieto, G. A., Tong, L., Sears‐Kraxberger, I., Rice, J. D., Steward, O., & Cotman, C. W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568659 · Cited by 90 · see citing works
Di Domenico, F., Tramutola, A., Foppoli, C., Head, E., Perluigi, M., & Butterfield, D. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.009 · Cited by 89 · see citing works
Ménard, C., Bastianetto, S., & Quirion, R. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00281 · Cited by 87 · see citing works
Giovannini, M. G., Lana, D., & Pepeu, G. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.12.014 · Cited by 87 · see citing works
Yang, W., Zhou, X., Zimmermann, H. R., Cavener, D. R., Klann, E., & Ma, T. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.005 · Cited by 87 · see citing works
Self-citationMitochondrial dysfunction and neurological disorders: A narrative review and treatment overview
Alshial, E. E., Abdulghaney, M. I., Wadan, A. S., Abdellatif, M. A., Ramadan, N. E., Suleiman, A. M., Waheed, N., Abdellatif, M., & Mohammed, H. S. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122257 · Cited by 89 · see citing works
Amyloid-β Oligomers Induce Differential Gene Expression in Adult Human Brain Slices
Sebollela, A. S., Freitas-Corrêa, L., de Oliveira, F. F., Paula-Lima, A. C., Saraiva, L. M., Martins, S. M., Mota, L. D. C., Torres, C., Alves‐Leon, S. V., de Souza, J. M., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.298471 · Cited by 86 · see citing works
Defective proteostasis in Alzheimer’s disease
Cozachenco, D., Ribeiro, F. C., & Ferreira, S. T. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101862 · Cited by 84 · see citing works
Taking aim at Alzheimer's disease through the mammalian target of rapamycin
Maiese, K. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.941921 · Cited by 82 · see citing works
Early Life Stress and Epigenetics in Late-onset Alzheimer’s Dementia: A Systematic Review
Lemche, E. (2018) · Current Genomics · doi:10.2174/1389202919666171229145156 · Cited by 82 · see citing works
Mody, N., Agouni, A., Mcilroy, G. D., Platt, B., & Delibegović, M. (2011) · Diabetologia · doi:10.1007/s00125-011-2160-2 · Cited by 79 · see citing works
Pignataro, G., Capone, D., Polichetti, G., Vinciguerra, A., Gentile, A., Renzo, G. D., & Annunziato, L. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.05.003 · Cited by 79 · see citing works
Driving neural regeneration through the mammalian target of rapamycin
Maiese, K. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.139453 · Cited by 79 · see citing works
Inflammation, insulin signaling and cognitive function in aged APP/PS1 mice
Denver, P., English, A. R., & McClean, P. L. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.03.032 · Cited by 78 · see citing works
Ma, T., Tzavaras, N., Tsokas, P., Landau, E. M., & Blitzer, R. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4761-11.2011 · Cited by 77 · see citing works
Self-citationHampel, H. J., Schneider, L. S., Giacobini, E., Kivipelto, M., Sindi, S., Dubois, B., Broich, K., Nisticò, R., Aisen, P. S. S., & Lista, S. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.995637 · Cited by 77 · see citing works
Dysfunction of the mTOR pathway is a risk factor for Alzheimer's disease
Yates, S. C., Zafar, A., Hubbard, P., Nagy, S., Durant, S., Bicknell, R., Wilcock, G., Christie, S., Esiri, M. M., Smith, A. D., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-3 · Cited by 76 · see citing works
Memantine: Updating a rare success story in pro-cognitive therapeutics
Tari, P. K., Parsons, C. G., Collingridge, G. L., & Rammes, G. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109737 · Cited by 75 · see citing works
Chen, S., Zhang, B., Wang, Y., Li, H., Xiong, R., Zhao, Z., Chu, X., Li, Q., & Sun, S. (2016) · Drug Design Development and Therapy · doi:10.2147/dddt.s99958 · Cited by 75 · see citing works
Astrocytes and synaptic plasticity in health and disease
Singh, A., & Abraham, W. C. (2017) · Experimental Brain Research · doi:10.1007/s00221-017-4928-1 · Cited by 75 · see citing works
Gureev, A. P., Popov, V. N., & Starkov, A. A. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113285 · Cited by 73 · see citing works
Wong, W. T., Dresner, S., Forooghian, F., Glaser, T. S., Doss, L. E., Zhou, M., Cunningham, D., Shimel, K. H., Harrington, M. W., Hammel, K., et al. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-11650 · Cited by 73 · see citing works
Lourenco, M. V., Ferreira, S. T., & Felice, F. G. D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.03.003 · Cited by 71 · see citing works
Tateda, S., Kanno, H., Ozawa, H., Sekiguchi, A., Yahata, K., Yamaya, S., & Itoi, E. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23328 · Cited by 71 · see citing works
Uddin, M. S., Rahman, M. A., Kabir, M. T., Behl, T., Mathew, B., Perveen, A., Barreto, G. E., Bin-Jumah, M. N., Abdel‐Daim, M. M., & Ashraf, G. M. (2020) · IUBMB Life · doi:10.1002/iub.2324 · Cited by 66 · see citing works
Subramanian, A., Tamilanban, T., Alsayari, A., Ramachawolran, G., Wong, L. S., Sekar, M., Gan, S. H., Subramaniyan, V., Chinni, S. V., Rani, N. N. I. M., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1094351 · Cited by 67 · see citing works
The mammalian target of rapamycin at the crossroad between cognitive aging and Alzheimer’s disease
Talboom, J. S., Velázquez, R., & Oddo, S. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.8 · Cited by 67 · see citing works
mTOR Hyperactivation in Down Syndrome Hippocampus Appears Early During Development
Iyer, A. M., van Scheppingen, J., Milenkovic, I., Anink, J. J., Adle-Biassette, H., Kovacs, G. G., & Aronica, E. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000083 · Cited by 69 · see citing works
Chen Shang, Y., Zhong Chong, Z., Wang, S., & Maiese, K. (2012) · Current Neurovascular Research · doi:10.2174/156720212803530618 · Cited by 66 · see citing works
GSK3 in Alzheimer's Disease: Mind the Isoforms
Ma, T. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131661 · Cited by 66 · see citing works
Self-citationBraidy, N., Essa, M. M., Poljak, A., Subash, S., Al‐Adawi, S., Manivasagm, T., Thenmozhi, A. J., Ooi, L., Sachdev, P. S., & Guillemin, G. J. (2016) · Oncotarget · doi:10.18632/oncotarget.10905 · Cited by 66 · see citing works
RetractedLithium as a Treatment for Alzheimer’s Disease: The Systems Pharmacology Perspective
Hampel, H. J., Lista, S., Mango, D., Nisticò, R., Perry, G. L., Ávila, J., Hernández, F., Geerts, H., Vergallo, A., (APMI), A. P. M. I., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190197 · Cited by 65 · see citing works
Li, Q., Navakkode, S., Rothkegel, M., Soong, T. W., Sajikumar, S., & Körte, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613700114 · Cited by 64 · see citing works
Cannabinoid Modulation of the Stressed Hippocampus
Scarante, F. F., Vila-Verde, C., Lopes, V. D., Ferreira‐Junior, N. C., Guimarães, F. S., & Campos, A. C. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00411 · Cited by 64 · see citing works
Zeng, Y., Zhang, J., Zhu, Y., Zhang, J., Shen, H., Lu, J., Pan, X., Lin, N., Dai, X., Zhou, M., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13056 · Cited by 63 · see citing works
The dark sides of amyloid in Alzheimer's disease pathogenesis
Sorrentino, P., Iuliano, A., Polverino, A., Jacini, F., & Sorrentino, G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2013.12.038 · Cited by 64 · see citing works
Role of Sirt1 During the Ageing Process: Relevance to Protection of Synapses in the Brain
Godoy, J. A., Zolezzi, J. M., Braidy, N., & Inestrosa, N. C. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8645-5 · Cited by 60 · see citing works
Yang, L., Zhang, J., Zheng, K., Shen, H., & Chen, X. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt091 · Cited by 62 · see citing works
Cutting through the Complexities of mTOR for the Treatment of Stroke
Maiese, K. (2014) · Current Neurovascular Research · doi:10.2174/1567202611666140408104831 · Cited by 61 · see citing works
Lawrence, J. L. M., Tong, M., Alfulaij, N., Sherrin, T., Contarino, M., White, M. M., Bellinger, F. P., Todorovic, C., & Nichols, R. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0326-14.2014 · Cited by 60 · see citing works
Neuroprotective Effects of Salidroside in a Mouse Model of Alzheimer’s Disease
Wang, H., Li, Q., Sun, S., & Chen, S. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00801-w · Cited by 59 · see citing works
Potential of GPCRs to modulate MAPK and mTOR pathways in Alzheimer’s disease
Franco, R., Martínez‐Pinilla, E., Navarro, G., & Zamarbide, M. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.004 · Cited by 59 · see citing works
Zhao, W., Wang, J., Bi, W., Ferruzzi, M. G., Yemul, S., Freire, D., Mazzola, P., Ho, L., Dubner, L., & Pasinetti, G. M. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.07.023 · Cited by 58 · see citing works
Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology.
Ruegsegger, C., Stucki, D. M., Steiner, S., Angliker, N., Radecke, J., Keller, É., Zuber, B., Rüegg, M., & Saxena, S. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.033 · Cited by 45 · see citing works
Rapamycin Responds to Alzheimer’s Disease: A Potential Translational Therapy
Hou, S.-J., Zhang, S., Li, Y., & Xu, S.-Y. (2023) · Clinical Interventions in Aging · doi:10.2147/cia.s429440 · Cited by 58 · see citing works
Lee, 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
Ye, X., Luo, H., Chen, Y., Wu, Q., Xiong, Y., Zhu, J., Diao, Y., Wu, Z., Miao, J., & Wan, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00210 · Cited by 56 · see citing works
- Authors
- Ma, T., Hoeffer, C. A., Capetillo-Zarate, E., Yu, F., Wong, H., Lin, M. T., Tampellini, D., Klann, E., Blitzer, R. D., & Gouras, G. K.
- Affiliations
- Weill Cornell Medicine (US)
- New York University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Gouras, Gunnar K.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-09-20
- Volume
- 5
- Issue
- 9
- Pages
- e12845
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2942840
- OpenAlex
- W2071279551
- Cited by
- 262
- References
- 52
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 7 · 2023: 13 · 2022: 13 · 2021: 20 · 2020: 26 · 2019: 10 · 2018: 11 · 2017: 14 · 2016: 18 · 2015: 17 · 2014: 30 · 2013: 23 · 2012: 22
- FWCI
- 13.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Communities in ADDI (University of the Basque Country) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Hispana (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health (N S03400 7, AG‐09464, AG28174)
- National Institute on Aging (R01AG027140, AG09464, R01AG020729, K02AG028174, AG28174, AG027140, P01AG009464)
- National Institute of General Medical Sciences (R01GM054508, GM-054508)
- National Institute of Neurological Disorders and Stroke (R37NS034007, R01NS034007, R29NS034007, NS-034007)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- mTOR signaling, Alzheimer's disease, synaptic plasticity, amyloid-beta, amyloid-beta 42, long-term potentiation, glycogen synthase kinase-3, GSK-3 inhibitors, FKBP12, hippocampus, synaptic dysfunction, intraneuronal amyloid-beta
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Humans, Mice, Inbred C57BL, Neuronal Plasticity, Peptide Fragments, Synapses, Signal Transduction, Amyloid beta-Peptides, Long-Term Potentiation, Mice, TOR Serine-Threonine Kinases
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