ArticleNature neuroscience2022
TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
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Who cites it
99 citing papers in PubMed, 157 citations in OpenAlex.
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- TREM2-mediated Crosstalk in ALS: Microglial Fate Transition, Protein Aggregate Clearance, and Peripheral Nerve Repair.Neuroscience bulletin · 2026Article
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Innate immune crosstalk in ALS/FTD pathogenesis.Cell insight · 2026Review
- Genetic suppression of myeloid receptor Clec7a attenuates microglia neuroinflammation and promotes microglial phagocytosis to delay disease progression in ALS models.bioRxiv : the preprint server for biology · 2026Article
- TREM2 Regulates Microglial Activation via the ERK/p38 Signaling Pathway: Implications for the Pathogenesis of Experimental Autoimmune Uveitis.Investigative ophthalmology & visual science · 2026Article
- Immune signaling and function in neurodegeneration.The Journal of clinical investigation · 2026Review
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- Chronic methanol exposure induces cognitive impairment and Alzheimer's-like pathology in rhesus monkeys.Animal models and experimental medicine · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Parkinson's disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses.NPJ Parkinson's disease · 2026Review
- Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?Frontiers in neurology · 2026Review
- The Neurogenic Niche: Interactions Among Vessels, Glia, and Neural Stem Cells.Stem cells international · 2026Review
- Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.ASN neuro · 2026Review
- Region-specific features of early glial activation and Aquaporin-4 dysregulation in conditional mouse models of TDP-43 proteinopathies.Discovery immunology · 2026Article
- Global research architecture of RNA-binding proteins in neurodegenerative diseases: a web of science bibliometric study with PubMed record verification, 2001-2025.Frontiers in aging neuroscience · 2026Article
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- Revisiting TREM2: from multi-omics signaling networks to clinical translation.Frontiers in immunology · 2026Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Triggering receptor expressed on myeloid cell 2 (TREM2) is linked to risk of neurodegenerative disease. However, the function of TREM2 in neurodegeneration is still not fully understood. Here, we investigated the role of microglial TREM2 in TAR DNA-binding protein 43 (TDP-43)-related neurodegeneration using virus-mediated and transgenic mouse models. We found that TREM2 deficiency impaired phagocytic clearance of pathological TDP-43 by microglia and enhanced neuronal damage and motor impairments. Mass cytometry analysis revealed that human TDP-43 (hTDP-43) induced a TREM2-dependent subpopulation of microglia with high CD11c expression and phagocytic ability. Using mass spectrometry (MS) and surface plasmon resonance (SPR) analysis, we further demonstrated an interaction between TDP-43 and TREM2 in vitro and in vivo as well as in human tissues from individuals with amyotrophic lateral sclerosis (ALS). We computationally identified regions within hTDP-43 that interact with TREM2. Our data highlight that TDP-43 is a possible ligand for microglial TREM2 and that this interaction mediates neuroprotection of microglia in TDP-43-related neurodegeneration.
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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.