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TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway
Zhong L, Zhang ZL, Li X, Liao C, Mou P, Wang T, Wang Z, Wang Z et al.. Frontiers in aging neuroscience, 2017-06-21
Topic: Brain proteins, microglia and lab models
DNAX-activating protein of 12 kDa (DAP12) is a signaling adapter protein expressed in cells that participate in innate immune responses. By pairing with different triggering receptors expressed on myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular responses. In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator.
Key findings
- By pairing with different triggering receptors expressed on myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular responses.
- In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator.
- TREM2 has also been shown to stimulate the phagocytosis of apoptotic neurons and define the barrier function in microglia.
- Notably, loss-of-function mutations of either DAP12 or TREM2 result in a disorder known as Nasu-Hakola disease (NHD); and mutations of these genes have been associated with the risk for Alzheimer's disease (AD), suggesting that TREM2 and DAP12 may regulate common signaling pathways in the disease pathogenesis.
Why it matters
This work describes how the TREM2/DAP12 complex influences microglial inflammatory responses through the JNK signaling pathway, noting that TREM2 acts as a negative regulator while TREM1 amplifies immune responses. Loss-of-function mutations in either DAP12 or TREM2 cause Nasu-Hakola disease, linking these molecules to brain disorders, but the study does not test any treatment or prevention approach for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 44/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (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 | 2 / 5 | 2017 — within 10 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 | 4 / 7 | Cited 84 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.6 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Xiao‐Fen Chen: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28680398) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
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Read the original
- DOI: 10.3389/fnagi.2017.00204
- PubMed: 28680398
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
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. 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.
APA 7th
Zhong, L., Zhang, Z. L., Li, X., Liao, C., Mou, P., Wang, T., et al. (2017). TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2017.00204
Vancouver
Zhong L, Zhang ZL, Li X, Liao C, Mou P, Wang T, et al. TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Frontiers in aging neuroscience. 2017. doi:10.3389/fnagi.2017.00204. PMID: 28680398.
BibTeX
@article{zhong2017-28680398,
author = {Zhong, L. and Zhang, Z. L. and Li, X. and Liao, C. and Mou, P. and Wang, T. and Wang, Z. and others},
title = {{TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway}},
journal = {Frontiers in aging neuroscience},
year = {2017},
doi = {10.3389/fnagi.2017.00204},
pmid = {28680398},
url = {https://doi.org/10.3389/fnagi.2017.00204}
}
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