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Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases
Konishi H, Kiyama H.. Frontiers in cellular neuroscience, 2018-08-06
Topic: Brain proteins, microglia and lab models
Microglia are activated after neuronal injury and in neurodegenerative diseases, and trigger neuroinflammation in the central nervous system (CNS). Microglia-derived neuroinflammation has both beneficial and detrimental effects on neurons. Because the timing and magnitude of microglial activation is thought to be a critical determinant of neuronal fate, understanding the molecular mechanisms underlying microglial activation is required to enable establishment of microglia-targeted therapies for neural diseases.
Key findings
- Microglia-derived neuroinflammation has both beneficial and detrimental effects on neurons.
- Because the timing and magnitude of microglial activation is thought to be a critical determinant of neuronal fate, understanding the molecular mechanisms underlying microglial activation is required to enable establishment of microglia-targeted therapies for neural diseases.
- Plasma membrane receptors play primary roles as activators of microglia and in this review, we focus on a receptor complex involving triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12), both of which are causative genes for Nasu-Hakola disease, a dementia with bone cysts.
- Recent transcriptome approaches demonstrated TREM2/DAP12 signaling as the principal regulator that transforms microglia from a homeostatic to a neural disease-associated state.
Why it matters
This review explains that microglia-driven inflammation can be both helpful and harmful to neurons, and that timing and amount of microglial activation may decide whether neurons survive. It argues that understanding how microglia are activated is needed before microglia-targeted therapies can be developed.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 cellular neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Cellular Neuroscience: journal h-index 175 (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 | 2018 — 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 | 6 / 7 | Cited 300 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 30.0 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 8.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 3 / 4 | Cited 126 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hiroshi Kiyama: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Nagoya University: institution h-index 758 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30127720) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fncel.2018.00206
- PubMed: 30127720
- Original source →
- Free full text: Frontiers in Cellular 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. Check the citation against the original before you use it.
APA 7th
Konishi, H., & Kiyama, H. (2018). Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. Frontiers in cellular neuroscience. https://doi.org/10.3389/fncel.2018.00206
Vancouver
Konishi H, Kiyama H. Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. Frontiers in cellular neuroscience. 2018. doi:10.3389/fncel.2018.00206. PMID: 30127720.
BibTeX
@article{konishi2018-30127720,
author = {Konishi, H. and Kiyama, H.},
title = {{Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases}},
journal = {Frontiers in cellular neuroscience},
year = {2018},
doi = {10.3389/fncel.2018.00206},
pmid = {30127720},
url = {https://doi.org/10.3389/fncel.2018.00206}
}
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