ReviewFrontiers in cellular neuroscience2018
Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases.
Review in Frontiers in cellular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
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Who cites it
190 citing papers in PubMed, 305 citations in OpenAlex.
- Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study of Iluzanebart in Healthy Volunteers.Annals of clinical and translational neurology · 2025Trial
- Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease.Pharmacology research & perspectives · 2019Trial
- The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective.Basic & clinical pharmacology & toxicology · 2026Review
- TREM2 Attenuates Microglial Pyroptosis in Sepsis-Associated Encephalopathy Through Modulation of the mtDNA-cGAS-STING Pathway.Molecular neurobiology · 2026Article
- The TREM2 R47H variant is associated with liver-plasma-brain axis dyshomeostasis in the 5xFAD mouse model of Alzheimer's disease.Neurobiology of aging · 2026Article
- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- TREM2-Targeting peptide tracer for neuroinflammation PET imaging.European journal of nuclear medicine and molecular imaging · 2026Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Role Shift of Glial Cells from Physiology to Pathology in Alzheimer's Disease: The Regulatory Impact of Exercise.Neuroscience bulletin · 2026Review
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- TLR7-induced murine inflammation results in a global neuroinflammatory response driving neural circuit-specific transcriptomic changes.Scientific reports · 2026Article
- The impact of Trem2-mediated macrophage polarization on the mechanisms of allergic rhinitis.Scientific reports · 2026Article
- Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury.Journal of neuroinflammation · 2026Article
- The role of DAP12 in immune-related inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Revisiting the Peripheral Nerve Injury and Regeneration.Neuromolecular medicine · 2026Review
- Trem2 exacerbates ischemic brain injury through Gpnmb in a photothrombotic stroke model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- β-Asarone Mediates the Alleviation of Neuroinflammation in Alzheimer's Disease Via Modulation of the TREM2/PI3K/AKT Signaling Pathway.Inflammation · 2026Article
- A ligand-mimetic anti-TREM2 agonist antibody elevates soluble TREM2 and ameliorates pathology in mouse models of Alzheimer's disease and multiple sclerosis.Journal of neuroinflammation · 2026Article
- Immune cell dynamics in neurological disorders: from inflammation to microgliopathy and Neuron-Glia crosstalk.Molecular biology reports · 2026Review
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. 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. Furthermore, animal model studies revealed critical roles for TREM2/DAP12 in the regulation of microglial activity, including survival, phagocytosis, and cytokine production, not only in Alzheimer's disease but also in other neural diseases, such as Parkinson's disease, demyelinating disease, ischemia, and peripheral nerve injury. Intriguingly, while TREM2/DAP12-mediated microglial activation is detrimental for some diseases, including peripheral nerve injury, it is beneficial for other diseases. As the role of activated microglia differs among disease models, TREM2/DAP12 signaling may result in different outcomes in different diseases. In this review we discuss recent perspectives on the role of TREM2/DAP12 in microglia and their contribution to neural diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.