Cited by 1,033Alzheimer's disease research and treatmentsAutophagy in Disease and TherapyDementia and Cognitive Impairment Research

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Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease

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Spilman, Patricia, Podlutskaya, Natalia, Hart, Matthew J., Debnath, Jayanta, Gorostiza, Olivia, Bredesen, Dale, Richardson, Arlan, Strong, Randy, Galvan, Veronica·2010·PLoS ONE

DOI 10.1371/journal.pone.0009979PMC PMC2848616

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Abstract

BACKGROUND: Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. METHODOLOGY/PRINCIPAL FINDINGS: We used rapamycin administration and behavioral tools in a mouse model of AD as well as standard biochemical and immunohistochemical measures in brain tissue to provide answers for this question. Here we show that long-term inhibition of mTOR by rapamycin prevented AD-like cognitive deficits and lowered levels of Abeta(42), a major toxic species in AD[7], in the PDAPP transgenic mouse model. These data indicate that inhibition of the mTOR pathway can reduce Abeta(42) levels in vivo and block or delay AD in mice. As expected from the inhibition of mTOR, autophagy was increased in neurons of rapamycin-treated transgenic, but not in non-transgenic, PDAPP mice, suggesting that the reduction in Abeta and the improvement in cognitive function are due in part to increased autophagy, possibly as a response to high levels of Abeta. CONCLUSIONS/SIGNIFICANCE: Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD.

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Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
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
Self-citation
p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276
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 2,365
Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
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
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953
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Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892

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Kim, S., Cho, Y.-S., Kim, Y., Park, J., Yoo, S., Gwak, J., Kim, Y., Gwon, Y., Kam, T., & Jung, Y. (2023) · Autophagy · doi:10.1080/15548627.2023.2181614 · Cited by 65
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Cheng, C., Lin, M.-J., & Shen, C.-K. J. (2015) · Journal of Neurogenetics · doi:10.3109/01677063.2015.1077832 · Cited by 66
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Correia, S. C., Resende, R., Moreira, P. I., & Pereira, C. (2015) · DNA and Cell Biology · doi:10.1089/dna.2014.2757 · Cited by 66
Wogonin increases β-amyloid clearance and inhibits tau phosphorylation via inhibition of mammalian target of rapamycin: potential drug to treat Alzheimer’s disease
Zhu, Y., & Wang, J. (2015) · Neurological Sciences · doi:10.1007/s10072-015-2070-z · Cited by 64
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Xu, Y., Tian, C., Wang, S.-B., Xie, W.-L., Guo, Y., Zhang, J., Shi, Q., Chen, C., & Dong, X. (2012) · Autophagy · doi:10.4161/auto.21482 · Cited by 66
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Tuberous Sclerosis Protein 2 (TSC2) Modulates CCN4 Cytoprotection During Apoptotic Amyloid Toxicity in Microglia
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“Although the presence of TSC2 may foster cell protection with WISP1 through pathways that may limit excessive mTOR activity similar to observations with autophagic cell survival [43] and in models of AD [54], we show that TSC2 also is necessary for WISP1 to control Shang et al.”
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Hinojosa, C. A., Mgbemena, V. E., Roekel, S. V., Austad, S. N., Miller, R. A., Bose, S., & Orihuela, C. J. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.013 · Cited by 61
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Sebold, A. J., Day, A. M., Ewen, J. B., Adamek, J. H., Byars, A. W., COHEN, B. A., Kossoff, E. H., Mizuno, T., Ryan, M., Sievers, J. W., et al. (2020) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2020.10.013 · Cited by 59
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Checler, F., Afram, E., Pardossi‐Piquard, R., & Lauritzen, I. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100489 · Cited by 63
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Yang, Y., & Zhang, L. (2020) · Food & Function · doi:10.1039/c9fo02611h · Cited by 57
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Franco, R., Martínez‐Pinilla, E., Navarro, G., & Zamarbide, M. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.004 · Cited by 61
Proteostasis disturbance in amyotrophic lateral sclerosis
Medinas, D. B., Valenzuela, V., & Hetz, C. A. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx274 · Cited by 67
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Malampati, S., Song, J., Tong, B. C., Nalluri, A., Yang, C., Wang, Z., Sreenivasmurthy, S. G., Zhu, Z., Liu, J., Su, C.-F., et al. (2020) · Cells · doi:10.3390/cells9020311 · Cited by 60
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Meng, T., Lin, S., Zhuang, H., Huang, H., He, Z., Hu, Y., Gong, Q., & Feng, D. (2019) · Cell Stress · doi:10.15698/cst2019.05.186 · Cited by 58
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Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
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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
Hippocampal Endosomal, Lysosomal, and Autophagic Dysregulation in Mild Cognitive Impairment
Perez, S. E., He, B., Nadeem, M., Wuu, J., Ginsberg, S. D., Ikonomović, M. D., & Mufson, E. J. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000179 · Cited by 57
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Metabolism navigates neural cell fate in development, aging and neurodegeneration
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DNA methylation and cognitive aging
Xu, X. Z. S. (2015) · Oncotarget · doi:10.18632/oncotarget.4215 · Cited by 57
Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders
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Authors: Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V.
Affiliations: Buck Institute for Research on Aging (US)
The University of Texas at San Antonio Health Science Center (US)
University of California, San Francisco (US)
ORCID: Spilman, Patricia
Hart, Matthew J.
Debnath, Jayanta
Bredesen, Dale
Richardson, Arlan
Strong, Randy
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2010-04-01
Volume: 5
Issue: 4
Pages: e9979
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0009979
PMC: PMC2848616
OpenAlex: W2037653131
Cited by: 1,033
References: 52
Citations by year: 2026: 46 · 2025: 50 · 2024: 41 · 2023: 63 · 2022: 61 · 2021: 75 · 2020: 91 · 2019: 82 · 2018: 72 · 2017: 57 · 2016: 68 · 2015: 75 · 2014: 72 · 2013: 62 · 2012: 58
FWCI: 39.00
Type: journal article
Language: en
Update notices: correction (2011-12-27)
correction (2011-11-18)
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship (California Digital Library) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: U.S. Department of Veterans Affairs
Alzheimer's Association (NIRG-DDC-120433)
Buck Institute for Research on Aging
University of Texas Health Science Center at San Antonio
National Institute on Aging (P30AG13319, P30AG013319, U01AG022307)
National Cancer Institute (R01CA126792)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: rapamycin, mTOR inhibition, Alzheimer's disease, amyloid-beta 42, cognitive impairment, autophagy, lifespan extension, neuroprotection, therapeutic target
MeSH terms: Aging, Alzheimer Disease, Animals, Autophagy, Cognition Disorders, Disease Models, Animal, Immunosuppressive Agents, Signal Transduction, Amyloid beta-Peptides, Sirolimus, Mice, TOR Serine-Threonine Kinases

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Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease

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