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Beyond Glycemic Control: The Pleiotropic Role of GLP-1RAs and Melatonin in Combating Neuroinflammation and Mitochondrial Dysfunction
Reiter RJ, Sharma R, Simão VA, Chuffa LGdA, Carloni S, Gentile C, Balduini W, Manucha W.. Preprints.org, 2026-10-28
Topic: Gut, metabolism and diet
Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein homeostasis form interconnected pathological networks in acute central nervous system injury and chronic neurodegenerative disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for metabolic disorders, exhibit neuroprotective activity in experimental models through effects on neuronal survival, metabolic adaptation, and inflammatory signaling. Melatonin complements these actions through mitochondrial redox protection, preservation of bioenergetics, and circadian regulation. This narrative review examines the pharmacological diversity and central nervous system accessibility of GLP-1RAs, including emerging multi-receptor agonists, and their convergence with melatonin on AMPK, sirtuin–PGC-1α, and mitochondrial quality-control networks. Evidence from stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes-associated cognitive decline highlights opportunities to translate these mechanisms into neuroprotective strategies. Experimental efficacy, exploratory cognitive findings, and existing clinical experience provide a foundation for further investigation, while heterogeneous clinical outcomes help define appropriate populations, endpoints, and treatment conditions. A mitochondrial-support framework is proposed in which melatonin may preserve the cellular environment needed for GLP-1RA-mediated metabolic and survival responses. Together, these complementary mechanisms provide a promising foundation for developing combined GLP-1RA–melatonin strategies to preserve mitochondrial function, attenuate neuroinflammation, and support cognitive and functional recovery.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Reiter, R. J., Sharma, R., Simão, V. A., LGdA, C., Carloni, S., Gentile, C., et al. (2026). Beyond Glycemic Control: The Pleiotropic Role of GLP-1RAs and Melatonin in Combating Neuroinflammation and Mitochondrial Dysfunction. Preprints.org. https://doi.org/10.20944/preprints202610.2789.v1
Vancouver
Reiter RJ, Sharma R, Simão VA, LGdA C, Carloni S, Gentile C, et al. Beyond Glycemic Control: The Pleiotropic Role of GLP-1RAs and Melatonin in Combating Neuroinflammation and Mitochondrial Dysfunction. Preprints.org. 2026. doi:10.20944/preprints202610.2789.v1.
BibTeX
@article{reiter2026-d34fac97,
author = {Reiter, R. J. and Sharma, R. and Simão, V. A. and LGdA, Chuffa and Carloni, S. and Gentile, C. and Balduini, W. and Manucha, W.},
title = {{Beyond Glycemic Control: The Pleiotropic Role of GLP-1RAs and Melatonin in Combating Neuroinflammation and Mitochondrial Dysfunction}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202610.2789.v1},
url = {https://doi.org/10.20944/preprints202610.2789.v1}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- This narrative review examines the pharmacological diversity and central nervous system accessibility of GLP-1RAs, including emerging multi-receptor agonists, and their convergence with melatonin on AMPK, sirtuin–PGC-1α, and mitochondrial quality-control networks.
- Evidence from stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes-associated cognitive decline highlights opportunities to translate these mechanisms into neuroprotective strategies.
- Experimental efficacy, exploratory cognitive findings, and existing clinical experience provide a foundation for further investigation, while heterogeneous clinical outcomes help define appropriate populations, endpoints, and treatment conditions.
- A mitochondrial-support framework is proposed in which melatonin may preserve the cellular environment needed for GLP-1RA-mediated metabolic and survival responses.
- Together, these complementary mechanisms provide a promising foundation for developing combined GLP-1RA–melatonin strategies to preserve mitochondrial function, attenuate neuroinflammation, and support cognitive and functional recovery.
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Study details
- Study designnarrative review
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | Design recorded as “narrative review”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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