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Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation
Fremuth LE, Hu H, van de Vlekkert D, Annunziata I, Weesner JA, Alessandra d'Azzo.. Cell reports, 2025-01-14
Topic: Brain proteins, microglia and lab models
Neuraminidase 1 (NEU1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, NEU1 regulates immune cells, primarily those of the monocytic lineage. Here, we examine how Neu1 influences microglia by modulating the sialylation of full-length Trem2 (Trem2-FL), a multifunctional receptor that regulates microglial survival, phagocytosis, and cytokine production.
Key findings
- As such, NEU1 regulates immune cells, primarily those of the monocytic lineage.
- Here, we examine how Neu1 influences microglia by modulating the sialylation of full-length Trem2 (Trem2-FL), a multifunctional receptor that regulates microglial survival, phagocytosis, and cytokine production.
- When Neu1 is deficient/downregulated, Trem2-FL remains sialylated, accumulates intracellularly, and is excessively cleaved into a C-terminal fragment (Trem2-CTF) and an extracellular soluble domain (sTrem2), enhancing their signaling capacities.
- Sialylated Trem2-FL (Sia-Trem2-FL) does not hinder Trem2-FL-DAP12-Syk complex assembly but impairs signal transduction through Syk, ultimately abolishing Trem2-dependent phagocytosis.
Why it matters
This laboratory work describes how the enzyme Neu1 affects microglia by changing sialylation of the Trem2 receptor. It is basic cell research about a possible mechanism and does not test any treatment in people.
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Study details
- Evidence strengthLow
How this study scored 46/100
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 senior author's track record, so that was left out: it earned 44 of the 96 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| Journal's citation record | 3 / 4 | Cell Reports: journal h-index 321 (OpenAlex, 2026-10-29) |
| 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 | 3 / 7 | Cited 27 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 8.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Alessandra d'Azzo holds only 3 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | St. Jude Children's Research Hospital: institution h-index 942 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39817909) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 44 of the 96 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Fremuth, L. E., Hu, H., van de Vlekkert, D., Annunziata, I., Weesner, J. A., & d'Azzo, A. (2025). Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation. Cell reports. https://doi.org/10.1016/j.celrep.2024.115204
Vancouver
Fremuth LE, Hu H, van de Vlekkert D, Annunziata I, Weesner JA, d'Azzo A. Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation. Cell reports. 2025. doi:10.1016/j.celrep.2024.115204. PMID: 39817909.
BibTeX
@article{fremuth2025-39817909,
author = {Fremuth, L. E. and Hu, H. and van de Vlekkert, D. and Annunziata, I. and Weesner, J. A. and d'Azzo, Alessandra},
title = {{Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation}},
journal = {Cell reports},
year = {2025},
doi = {10.1016/j.celrep.2024.115204},
pmid = {39817909},
url = {https://doi.org/10.1016/j.celrep.2024.115204}
}
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