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Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease
Carmela Gallo, Lucia Verrillo, Emiliano Manzo, Emma Cauzzi, Livia La Barbera, Giuseppina Sabatino, Maria Luisa De Paolis, Michele Francesco Maria Sciacca et al.. Journal of neuroinflammation, 2025-12-13
Topic: Inflammation, microglia and astrocytes
We demonstrate that the small-molecule TREM2 ligand SULF A functions as an immunomodulator that reprograms microglia toward a reparative phenotype. It promotes a ramified and polarized microglial morphology associated with enhanced cellular motility, phagocytic capacity and clearance of neurotoxic Aβ peptides. SULF A upregulates arginase expression, downregulates inducible Nitric Oxide Synthase (iNOS), and redirects microglial metabolism toward tissue-protective functions. This phenotypic shift is characterized by increased TREM2 turnover and upregulation of CD68 and CCL2, without triggering classical inflammatory hallmarks. In vivo, SULF A enhances plaque‑associated microglial recruitment, reduces plaque burden, preserves midbrain dopaminergic neurons, and improves cognitive and motivational performance in Tg2576 mice. We propose that SULF A is a promising therapeutic small molecule that restores microglial homeostasis via an inflammation-sparing mechanism. It enhances amyloid clearance, preserves vulnerable neurons, and improves cognitive function in vivo. These findings support SULF A as a disease-modifying approach that extends beyond conventional plaque-targeting strategies in AD.
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APA 7th
Gallo, C., Verrillo, L., Manzo, E., Cauzzi, E., La Barbera, L., Sabatino, G., et al. (2025). Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease. Journal of neuroinflammation. https://doi.org/10.1186/s12974-025-03634-w
Vancouver
Gallo C, Verrillo L, Manzo E, Cauzzi E, La Barbera L, Sabatino G, et al. Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease. Journal of neuroinflammation. 2025. doi:10.1186/s12974-025-03634-w. PMID: 41390810.
BibTeX
@article{gallo2025-41390810,
author = {Gallo, Carmela and Verrillo, Lucia and Manzo, Emiliano and Cauzzi, Emma and La Barbera, Livia and Sabatino, Giuseppina and De Paolis, Maria Luisa and Sciacca, Michele Francesco Maria and others},
title = {{Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease}},
journal = {Journal of neuroinflammation},
year = {2025},
doi = {10.1186/s12974-025-03634-w},
pmid = {41390810},
url = {https://doi.org/10.1186/s12974-025-03634-w}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- We demonstrate that the small-molecule TREM2 ligand SULF A functions as an immunomodulator that reprograms microglia toward a reparative phenotype.
- It promotes a ramified and polarized microglial morphology associated with enhanced cellular motility, phagocytic capacity and clearance of neurotoxic Aβ peptides.
- SULF A upregulates arginase expression, downregulates inducible Nitric Oxide Synthase (iNOS), and redirects microglial metabolism toward tissue-protective functions.
- This phenotypic shift is characterized by increased TREM2 turnover and upregulation of CD68 and CCL2, without triggering classical inflammatory hallmarks.
- In vivo, SULF A enhances plaque‑associated microglial recruitment, reduces plaque burden, preserves midbrain dopaminergic neurons, and improves cognitive and motivational performance in Tg2576 mice.
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Study details
- Evidence strengthLow
How this study scored 43/100
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuroinflammation) |
| 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 | 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 41390810) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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