Activated mTOR and PKR Kinases in Lymphocytes Correlate with Memory and Cognitive Decline in Alzheimer’s Disease
Abstract
Background The control of translation, involving the kinases mTOR (mammalian target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase), modulates cell survival and death and is altered in the brains of patients with Alzheimer's disease (AD). In AD increased susceptibility of lymphocytes to apoptosis has been reported. Methods We investigated the level of the kinases mTOR and PKR and the eukaryotic initiation factor 2alpha (eIF2alpha) in lymphocytes of patients with AD in comparison with controls. In AD patients we also looked for a correlation between activated proteins and cognitive and memory tests. Results We report significant alterations of the levels of these kinases and eIF2alpha in lymphocytes of AD patients that were also significantly correlated with cognitive and memory test scores. Conclusion These results suggest that the levels of mTOR, PKR and eIF2alpha in lymphocytes could follow the cognitive decline in AD.
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PKR and eIF2α levels were negatively correlated with cognitive and memory test scores in AD patients, with higher PKR expression associated with lower cognitive test scores.
“These modifications were significantly correlated with cognitive and memory test scores performed in AD patients.”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [101]
In patients, PKR levels were correlated to the severity of the disease.
“In patients, the PKR levels were correlated to the severity of the disease [101].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [101]
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 1× · see citing works
“The initial control of protein translation comprises 2 main signaling pathways, including the kinases mTOR (mammalian target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase) [”
BackgroundGriffin, 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
Li, X., Alafuzoff, I., Soininen, H., Winblad, B., & Pei, J. (2005) · The FEBS Journal · doi:10.1111/j.1742-4658.2005.04833.x · Cited by 324 · see citing works
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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
Agis-Torres, A., Sollhuber, M., Fernandez, M., & Sanchez-Montero, J. M. (2014) · Current Neuropharmacology · doi:10.2174/1570159x113116660047 · Cited by 202 · 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-citationDamjanac, 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
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- Authors
- Paccalin, M., Pain-Barc, S., Pluchon, C., Paul, C., Besson, M.-N., Carret-Rebillat, A.-S., Rioux-Bilan, A., Gil, R., & Hugon, J.
- Affiliations
- Université de Poitiers (FR)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 2006
- Volume
- 22
- Issue
- 4
- Pages
- 320-326
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W1974034152
- Cited by
- 96
- References
- 4
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Alzheimer's disease, mTOR, PKR, eIF2α, lymphocytes, translational regulation, cognitive decline, memory decline, apoptosis, biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Cognition, Female, Humans, Lymphocytes, Male, Memory, Phosphorylation, Protein Kinases, Biomarkers, Eukaryotic Initiation Factor-2, Disease Progression, eIF-2 Kinase, TOR Serine-Threonine Kinases
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