mTOR/p70S6k signalling alteration by Aβ exposure as well as in APP‐PS1 transgenic models and in patients with Alzheimer's disease
Abstract
In Alzheimer's disease, neuropathological hallmarks include the accumulation of beta-amyloid peptides (Abeta) in senile plaques, phosphorylated tau in neurofibrillary tangles and neuronal death. Abeta is the major aetiological agent according to the amyloid cascade hypothesis. Translational control includes phosphorylation of the kinases mammalian target of rapamycin (mTOR) and p70S6k which modulate cell growth, proliferation and autophagy. It is mainly part of an anti-apoptotic cellular signalling. In this study, we analysed modifications of mTOR/p70S6k signalling in cellular and transgenic models of Alzheimer's disease, as well as in lymphocytes of patients and control individuals. Abeta 1-42 produced a rapid and persistent down-regulation of mTOR/p70S6k phosphorylation in murine neuroblastoma cells associated with caspase 3 activation. Using western blottings, we found that phosphorylated forms of mTOR and p70S6k are decreased in the cortex but not in the cerebellum (devoid of plaques) of double APP/PS1 transgenic mice compared with control mice. These results were confirmed by immunohistochemical methods. Finally, the expression of phosphorylated p70S6k was significantly reduced in lymphocytes of Alzheimer's patients, and levels of phosphorylated p70S6k were statistically correlated with Mini Mental Status Examination (MMSE) scores. Taken together, these findings demonstrate that the mainly anti-apoptotic mTOR/p70S6k signalling is altered in cellular and transgenic models…
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Aβ exposure induces a sustained reduction of mTOR/p70S6K signalling in neuroblastoma cell cultures.
“Aβ exposure induces a sustained reduction of mTOR/p70S6K signalling in neuroblastoma cell cultures marked by a progressive decrease of phosphorylated mTOR and phosphorylated p70S6K [27, 89].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [27]
In lymphocytes of AD patients, the PT389-p70S6K/total p70S6K ratio was reduced compared to control individuals and levels were positively correlated with MMSE scores.
“Furthermore, in the lymphocytes of AD patients the PT389-p70S6K/total p70S6K ratio was reduced in AD patients (n= 26) compared to control individuals (n= 28) and levels were positively correlated with Mini Mental Status Examination (MMSE) scores [27].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [27]
Cites
Ribosomal S6 Kinase Signaling and the Control of Translation
Dufner, A., & Thomas, G. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4683 · Cited by 676 · cited 3× · see citing works
“mTOR can also phosphorylate kinase p70S6k that stimulates protein synthesis (Dufner and Thomas 1999).”
BackgroundChang, 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
Self-citationLymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease
Mecocci, P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.5.794 · Cited by 229 · see citing works
Ferrer, I. (2002) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2002.t01-1-00410.x · Cited by 52 · see citing works
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Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · 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
Bordi, M., Berg, M. J., Mohan, P. S., Peterhoff, C. M., Alldred, M. J., Che, S., Ginsberg, S. D., & Nixon, R. A. (2016) · Autophagy · doi:10.1080/15548627.2016.1239003 · Cited by 353 · see citing works
Role of mTOR in physiology and pathology of the nervous system
Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338 · 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
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. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012845 · Cited by 262 · see citing works
Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer’s Disease
Shal, B., Ding, W., Ali, H., Kim, Y. S., & Khan, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00548 · Cited by 234 · see citing works
Carvalho, C., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.001 · Cited by 145 · 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
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
Hou, Y.-S., Guan, J.-J., Xu, H.-D., Wu, F., Sheng, R., & Qin, Z.-H. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00285-15 · Cited by 87 · see citing works
Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.
Tramutola, A., Lanzillotta, C., & Di Domenico, F. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1244482 · Cited by 69 · 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
Stanciu, G. D., Rusu, R. N., Bild, V., Filipiuc, L. E., Tamba, B.-I., & Ababei, D. C. (2021) · Biomedicines · doi:10.3390/biomedicines9050576 · Cited by 47 · see citing works
PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
Morel, M., Couturier, J., Lafay‐Chebassier, C., Paccalin, M., & Page, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00849.x · Cited by 47 · see citing works
Self-citationHong, B., Bea, S., Ko, H. Y., Kim, W. J., Cho, Y. M., & Shin, J.-Y. (2024) · Annals of Internal Medicine · doi:10.7326/m23-3220 · Cited by 33 · see citing works
Damjanac, M., Page, G., Ragot, S., Laborie, G., Gil, R., Hugon, J., & Paccalin, M. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00688.x · Cited by 31 · see citing works
Self-citationThe mTOR pathway: a common link between Alzheimer's disease and Down Syndrome
Wohlfert, A. J., Phares, J., & Granholm, A.-C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206183 · Cited by 6 · see citing works
- Authors
- Lafay‐Chebassier, C., Paccalin, M., Page, G., Barc‐Pain, S., Perault‐Pochat, M. C., Gil, R., Pradier, L., & Hugon, J.
- Affiliations
- Université de Poitiers (FR)
- Sanofi (France) (FR)
- Corresponding author
- Hugon, Jacques
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2005-06-10
- Volume
- 94
- Issue
- 1
- Pages
- 215-225
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2029308011
- Cited by
- 211
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 17 · 2019: 11 · 2018: 7 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 18 · 2013: 6 · 2012: 14
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre Hospitalier Universitaire de Poitiers
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, mTOR signaling, p70S6K phosphorylation, amyloid-beta, APP/PS1 mice, caspase-3 activation, apoptosis, lymphocytes, cognitive impairment, amyloid hypothesis, translational regulation, autophagy
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Female, Humans, Male, Membrane Proteins, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Protein Kinases, Signal Transduction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apoptosis, Ribosomal Protein S6 Kinases, 70-kDa, Cell Line, Tumor, Mice, Presenilin-1, TOR Serine-Threonine Kinases
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