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Effect of glycogen synthase kinase 3 β-mediated presenilin 1 phosphorylation on amyloid β production is negatively regulated by insulin receptor cleavage
Maesako M, Uemura K, Kubota M, Hiyoshi K, Ando K, Kuzuya A, Kihara T, Asada M et al.. Neuroscience, 2011-01-13
Topic: Brain proteins, microglia and lab models
Plain-language summary
Presenilin 1 (PS1), a causative molecule of familial Alzheimer's disease (AD), is known to be an unprimed substrate of glycogen synthase kinase 3 β (GSK3β) [Twomey and McCarthy (2006) FEBS Lett 580:4015-4020] and is phosphorylated at serine 353, 357 residues in its cytoplasmic loop region [Kirschenbaum et al. (2001) J Biol Chem 276:7366-7375]. In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results--PS1 phosphorylation increased amyloid β (Aβ) 42/40 ratio, and PS1 phosphorylation was enhanced in the human AD brains. Interestingly, we demonstrated that PS1 phosphorylation promoted insulin receptor (IR) cleavage and the IR intracellular domain (IR ICD) generated by γ-secretase led to a marked transactivation of Akt (PKB), which down-regulated GSK3β activity. Thus, the cleavage of IR by γ-secretase can inhibit PS1 phosphorylation in the long run. Taken together, our findings indicate that PS1 phosphorylation at serine 353, 357 residues can play a pivotal role in the pathology of AD and that the dysregulation of this mechanism may be causally associated with its pathology.
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APA 7th
Maesako, M., Uemura, K., Kubota, M., Hiyoshi, K., Ando, K., Kuzuya, A., et al. (2011). Effect of glycogen synthase kinase 3 β-mediated presenilin 1 phosphorylation on amyloid β production is negatively regulated by insulin receptor cleavage. Neuroscience. https://doi.org/10.1016/j.neuroscience.2010.12.017
Vancouver
Maesako M, Uemura K, Kubota M, Hiyoshi K, Ando K, Kuzuya A, et al. Effect of glycogen synthase kinase 3 β-mediated presenilin 1 phosphorylation on amyloid β production is negatively regulated by insulin receptor cleavage. Neuroscience. 2011. doi:10.1016/j.neuroscience.2010.12.017. PMID: 21238544.
BibTeX
@article{maesako2011-21238544,
author = {Maesako, M. and Uemura, K. and Kubota, M. and Hiyoshi, K. and Ando, K. and Kuzuya, A. and Kihara, T. and Asada, M. and others},
title = {{Effect of glycogen synthase kinase 3 β-mediated presenilin 1 phosphorylation on amyloid β production is negatively regulated by insulin receptor cleavage}},
journal = {Neuroscience},
year = {2011},
doi = {10.1016/j.neuroscience.2010.12.017},
pmid = {21238544},
url = {https://doi.org/10.1016/j.neuroscience.2010.12.017}
}
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Key findings
- In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results--PS1 phosphorylation increased amyloid β (Aβ) 42/40 ratio, and PS1 phosphorylation was enhanced in the human AD brains.
- Interestingly, we demonstrated that PS1 phosphorylation promoted insulin receptor (IR) cleavage and the IR intracellular domain (IR ICD) generated by γ-secretase led to a marked transactivation of Akt (PKB), which down-regulated GSK3β activity.
- Taken together, our findings indicate that PS1 phosphorylation at serine 353, 357 residues can play a pivotal role in the pathology of AD and that the dysregulation of this mechanism may be causally associated with its pathology.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21238544) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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