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Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes
Zhang M, Wu Y, Gao R, Chen X, Chen R, Chen Z.. Molecular and cellular endocrinology, 2021-12-11
Topic: Gut, metabolism and diet
Neuroinflammation is closely linked to the pathogenesis of Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) analogs exhibit anti-inflammatory and neuroprotective effects; hence, we investigated whether they reduce cognitive impairment and protect astrocytes from oxidative stress. We found that 5 × FAD transgenic mice treated with the synthetic GLP-1 receptor agonist exenatide had improved cognitive function per the Morris water maze test. Immunohistochemistry, western blotting, and ELISAs used to detect inflammatory factors revealed reduced neuroinflammation in extracted piriform cortexes of exenatide-treated mice as well as lower amyloid β 1-42 -induced oxidative stress and inflammation in astrocytes treated with exendin-4 (the natural analog of exenatide). Adenovirus-mediated overexpression of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 2 (NLRP2) revealed that exenatide/exendin-4 function may be attributed to NLRP2 inflammasome inhibition. Collectively, our results indicate that GLP-1 analogs improve cognitive dysfunction in vivo and protect astrocytes in vitro, potentially via the downregulation of the NLRP2 inflammasome.
Key findings
- We found that 5 × FAD transgenic mice treated with the synthetic GLP-1 receptor agonist exenatide had improved cognitive function per the Morris water maze test.
- Immunohistochemistry, western blotting, and ELISAs used to detect inflammatory factors revealed reduced neuroinflammation in extracted piriform cortexes of exenatide-treated mice as well as lower amyloid β 1-42 -induced oxidative stress and inflammation in astrocytes treated with exendin-4 (the natural analog of exenatide).
- Adenovirus-mediated overexpression of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 2 (NLRP2) revealed that exenatide/exendin-4 function may be attributed to NLRP2 inflammasome inhibition.
- Collectively, our results indicate that GLP-1 analogs improve cognitive dysfunction in vivo and protect astrocytes in vitro, potentially via the downregulation of the NLRP2 inflammasome.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / 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 multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular endocrinology) |
| 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 | 3 / 5 | 2022 — within 6 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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34906628) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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APA 7th
Zhang, M., Wu, Y., Gao, R., Chen, X., Chen, R., & Chen, Z. (2022). Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes. Molecular and cellular endocrinology. https://doi.org/10.1016/j.mce.2021.111529
Vancouver
Zhang M, Wu Y, Gao R, Chen X, Chen R, Chen Z. Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes. Molecular and cellular endocrinology. 2022. doi:10.1016/j.mce.2021.111529. PMID: 34906628.
BibTeX
@article{zhang2022-34906628,
author = {Zhang, M. and Wu, Y. and Gao, R. and Chen, X. and Chen, R. and Chen, Z.},
title = {{Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes}},
journal = {Molecular and cellular endocrinology},
year = {2022},
doi = {10.1016/j.mce.2021.111529},
pmid = {34906628},
url = {https://doi.org/10.1016/j.mce.2021.111529}
}
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