The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain
Abstract
The pathogenesis of formation of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains is unknown. One of the possibilities might be that translation of tau mRNA is aberrantly regulated in AD brains. In the current study, levels of various translation control elements including total and phosphorylated (p) forms of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), eukaryotic elongation factor 2 (eEF2), and eEF2 kinase were investigated in relationship with tau in homogenates of the medial temporal cortex from 20 AD and 10 control brains. We found that levels of p-mTOR (Ser2481), and p-4E-BP1 (Thr70 and Ser65) dramatically increase in AD, and are positively significantly correlated with total tau and p-tau. Levels of p-eEF2K were significantly increased, and total eEF2 significantly decreased in AD, when compared to controls. The changes of p-mTOR (2481), p-4E-BP1, and p-eEF2 were immunohistochemically confirmed to be in neurons of AD brains. This suggested that there are obvious abnormalities of elements related with translation control in AD brain and their aberrant changes may up-regulate the translation of tau mRNA, contributing to hyperphosphorylated tau accumulation in NFT-bearing neurons.
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In the citing paper
“For example, mTORC1 and its downstream targets are hyperactive in human brains diagnosed with Alzheimer's disease (AD) (18 -20).”
In the citing paper
“Other studies showed significant increases of P-p70S6K (T389 and T421/S424), P-mTOR (S2481), P-eIF4E and P-4E-BP1 (T70 and S65) in homogenates of the medial temporal cortex in AD patients as compared to control brains [92, 93].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [92]
In the citing paper
“The levels of the mTOR signalling markers were significantly and positively correlated with total τ and P-t[92, 93].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [92]
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Metadata
- Authors
- Li, X., Alafuzoff, I., Soininen, H., Winblad, B., & Pei, J.
- Affiliations
- Karolinska Institutet (SE)
- Kuopio University Hospital (FI)
- Corresponding author
- Pei, Jin‐Jing
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2005-08
- Volume
- 272
- Issue
- 16
- Pages
- 4211-4220
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W1873073107
- Cited by
- 324
- References
- 27
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 13 · 2023: 15 · 2022: 28 · 2021: 23 · 2020: 24 · 2019: 22 · 2018: 14 · 2017: 19 · 2016: 21 · 2015: 18 · 2014: 22 · 2013: 16 · 2012: 11
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gun och Bertil Stohnes Stiftelse
- Alzheimerfonden
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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, tau protein, mTOR, 4E-BP1, elongation factor 2, eEF2 kinase, translational regulation, neurofibrillary tangles, tau hyperphosphorylation, medial temporal cortex, protein phosphorylation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Autoantibodies, Brain, Carrier Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Male, Middle Aged, Phosphoproteins, Phosphorylation, Protein Kinases, Case-Control Studies, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle Proteins, Peptide Elongation Factor 2, Adaptor Proteins, Signal Transducing, Elongation Factor 2 Kinase, TOR Serine-Threonine Kinases
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