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The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization
Elbadawy NN, Saad MA, Elfarrash S, Ahmed MAE, Abdelkader NF.. European journal of pharmacology, 2025-01-26
Topic: Brain proteins, microglia and lab models
Tau hyper-phosphorylation has been recognized as an essential contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies. In the last decade, tau hyper-phosphorylation has gained considerable concern in AD therapeutic development. Tauopathies are manifested with a broad spectrum of symptoms, from dementia to cognitive decline and motor impairments. Tau undergoes conformational changes and abnormal phosphorylation that mediate its detaching from microtubules, forming neurofibrillary tangles (NFTs). In the current study, a widely used P301S transgenic mice model of tauopathy was employed to evaluate the possible neuroprotective effects of semaglutide as an autophagy regulator through modifications of the brain renin-angiotensin system (RAS). Mice were divided into two groups according to their genotypes (wild type (Wt) and P301S), which were further subdivided to receive either vehicle (saline) or semaglutide (25 nmol/kg, i. p.), once every 2 days for 28 days. Current data suggest that semaglutide ameliorated the hyperactive pattern and alleviated the cognitive decline of P301S mice. It also hastened the autophagic flux through augmenting angiotensin-converting enzyme 2/sirtuin 1/forkhead box protein O1 signaling. Semaglutide also hindered the expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated glycogen synthase kinase-3 beta at serine 9, reducing the propagation of neuroinflammatory cytokines and oxidative reactions. Finally, semaglutide protected against hippocampal degeneration and reduced the immunoreactivity for total tau and ionized calcium-binding adapter molecule. Semaglutide showed promising neuroprotective implications in alleviating tauopathy-related AD's molecular and behavioral deficits through controlling autophagy and brain RAS.
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APA 7th
Elbadawy, N. N., Saad, M. A., Elfarrash, S., Ahmed, M. A. E., & Abdelkader, N. F. (2025). The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization. European journal of pharmacology. https://doi.org/10.1016/j.ejphar.2025.177305
Vancouver
Elbadawy NN, Saad MA, Elfarrash S, Ahmed MAE, Abdelkader NF. The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization. European journal of pharmacology. 2025. doi:10.1016/j.ejphar.2025.177305. PMID: 39875022.
BibTeX
@article{elbadawy2025-39875022,
author = {Elbadawy, N. N. and Saad, M. A. and Elfarrash, S. and Ahmed, M. A. E. and Abdelkader, N. F.},
title = {{The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization}},
journal = {European journal of pharmacology},
year = {2025},
doi = {10.1016/j.ejphar.2025.177305},
pmid = {39875022},
url = {https://doi.org/10.1016/j.ejphar.2025.177305}
}
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Key findings
- Current data suggest that semaglutide ameliorated the hyperactive pattern and alleviated the cognitive decline of P301S mice.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported 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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (European journal of pharmacology) |
| 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 | 4 / 5 | 2025 — within 3 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 | Laboratory or animal study (title names “mice”) — scores zero |
| 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 39875022) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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