Ask about this productRelated genes to: TREM2 Blocking Peptide
- Gene:
- TREM2 NIH gene
- Name:
- triggering receptor expressed on myeloid cells 2
- Previous symbol:
- -
- Synonyms:
- TREM-2, Trem2a, Trem2b, Trem2c
- Chromosome:
- 6p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-08-09
- Date modifiied:
- 2019-04-23
Related products to: TREM2 Blocking Peptide
Related articles to: TREM2 Blocking Peptide
- Microglia continuously survey the brain and shape neuronal activity, but their contribution to experience-dependent synaptic plasticity is unclear. Levodopa-induced dyskinesia (LID) is a disabling complication of late-stage Parkinson's disease (PD) that is linked to maladaptive striatal remodeling and is often assumed to reflect detrimental neuroinflammation. Here we identify a dyskinesia-associated microglial gene program in the striatum of PD patients and show that microglia instead act as a protective brake on LID. In a mouse model, microglial depletion exacerbated dyskinesia, whereas microglial repopulation mitigated it. Delivery of AAV expressing soluble TREM2 (sTREM2) similarly reduced LID without impairing the therapeutic benefit of levodopa. Single-nucleus transcriptomics revealed that microglial loss drives extensive remodeling of both direct and indirect spiny projection neurons (SPNs), while repopulation or sTREM2 reverses a large fraction of LID-associated transcriptional changes. Mechanistically, sTREM2 directly engages TrkB and potentiates BDNF-dependent TrkB-ERK signaling, consistent with positive allosteric modulation. Functionally, sTREM2 enhances BDNF-TrkB-dependent hippocampal synaptic plasticity and acutely rebalances striatal dendritic excitability in a compartment- and cell type-specific manner. These findings reveal an unexpected neuroimmune pathway in which microglia restrain maladaptive plasticity via sTREM2-TrkB signaling, with therapeutic implications. - Source: PubMed
Publication date: 2026/05/07
Castagnola CaitlinMarongiu RobertaWan YuansongTorres Eileen Ruth SFan LiJang Minwoo WendyCui QiaolingKim JihyeYe PearlyZhu JingjiePanichkina AlisaFall Alexandra BNorman KendraGao BeichenFoxe NessaWong Man YingZhu DaphneBhagwat MaitreyeeGong ShiaochingOrr Anna GLee Francis SSurmeier D JamesKaplitt Michael GGan Li - Neurotropic viruses disrupt brain homeostasis through complex interactions among infected cells, resident immune responses, and tissue architecture, yet how these processes unfold across space, time, and cell types, and how viral strain differences shape disease severity, remains poorly understood. Here, we integrate high-resolution spatial transcriptomics with infection-aware cell-type profiling to construct a spatiotemporal atlas of Zika virus (ZIKV) infection in the mouse brain. Comparing Asian and African ZIKV strains across early and late infection stages, we uncover structured, strain-dependent reorganization of immune and structural cell populations that defines discrete infection-associated tissue niches. Microglia undergo region-specific state transitions characterized by both cell-intrinsic antiviral programs and widespread bystander activation, producing tissue-wide immune amplification. In Asian strain infection, we identify disease-associated microglia (DAM) as critical mediators of infection containment: DAM accumulate in regions where viral burden stabilizes, are promoted by Apoe-Trem2 signaling from infected cells and are governed by transcription regulators that restrain inflammatory programs while preserving phagocytic and antiviral functions. In contrast, African strain infection is marked by impaired Apoe-Trem2 signaling, persistent inflammatory microglial activation, and failure of containment. Progressive infection leads to depletion of oligodendrocytes, astrocytes, and neurons, loss of local cellular diversity and disruption of tissue architecture concentrated in somatosensory and motor regions associated with myelination and synaptic programs. These architectural disruptions correlate with severe neurological phenotypes in African strain infection and are preceded by transcriptional dysregulation in infected glial cells, including sustained stress responses, inflammatory signaling, and suppression of myelination and homeostatic pathways. Together, our study establishes a spatially resolved framework linking viral strain-specific microglial states to tissue disorganization and neurological functional impairment, providing mechanistic insight into how neurotropic viruses reshape microenvironments to drive neurological disease. - Source: PubMed
Publication date: 2026/05/05
Hasib Md MusaddaqulMeng WenMena GonzaloHalloway HughRamos da Silva SuzaneKohanbash GaryHuang YufeiGao Shou-Jiang - Recurrent spontaneous abortion (RSA), the common early pregnancy complication, remains elusive in its pathogenesis and treatment. Recombinant humanized type III collagen (rhCOLIII), a novel biomaterial, has demonstrated efficacy in treating various diseases. However, the role of rhCOLIII in RSA is unclear. This study aimed to explore the therapeutic potential and underlying mechanisms of rhCOLIII in RSA at single-cell resolution. - Source: PubMed
Publication date: 2026/05/17
Dong ZhiyongWang LiDai JingcongYou ShuangLiu JiashuoZeng HuiWei QuanChen JiamingXing JieWang XinyiLiu ShuaibinDong XiaojingYang XiaHe FanHu Lina - Alzheimer's Disease (AD) is a major global health challenge, particularly in ageing populations, and current therapies offer limited modification of disease progression. Emerging evidence indicates that the gut microbiome contributes to AD pathogenesis through metabolic, immune, and neuroendocrine mechanisms. Microbial metabolites, including Short-Chain Fatty Acids (SCFAs), bile acids, and trimethylamine-N-oxide (TMAO), regulate neuronal signalling and blood-brain barrier integrity, and dysbiosis has been linked to amyloid-β (Aβ) accumulation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, and synaptic dysfunction. Host genetic factors, particularly APOE ε4 and immune-regulatory variants such as TREM2 and CD33, further influence microbial composition and susceptibility to metabolite-driven pathology. This review provides a deeper synthesis of current evidence by integrating findings across multi-omics studies and identifying key unresolved issues in the microbiome-AD field. The discussion evaluates whether microbiome alterations act as early initiators or downstream consequences of neurodegeneration, examines sources of heterogeneity in microbiome-targeted interventions, and considers how inter-individual variability in host genetics and microbial ecology may inform precision therapeutics. Conceptual frameworks presented here, including a two-phase dysbiosis trajectory and a metabolite "tipping-point" network, aim to reconcile conflicting results and support the development of testable mechanistic hypotheses. Microbiome-directed strategies, such as probiotics, prebiotics, dietary modulation, faecal microbiota transplantation, and antiviral therapies, demonstrate promise but require rigorous mechanistic validation and methodological standardisation. Continued advancement in longitudinal, genotype-stratified, and multi-omics research will be essential for translating microbiome science into clinically actionable approaches. Overall, current evidence positions the gut microbiome as a compelling frontier for the development of personalised, diseasemodifying strategies in AD. - Source: PubMed
Publication date: 2026/05/08
Saraswati Benedikta DiahWicaksono Agil WahyuValles Soraya LPoeggeler BurkhardSingh Sandeep Kumar - Diet quality, beyond total fat, may shape the immune tone of the brain in Alzheimer's-relevant contexts. We examined whether the fatty acid profile and food matrix of high-fat diets (HFD) modulate hippocampal neuroinflammation and explored target-level mechanisms with molecular docking. Male B6129SF2/J mice received a standard diet (SD) or HFD enriched with extra-virgin olive oil (EVOO), refined olive oil (ROO), refined palm oil (RPO), or ω3 long-chain polyunsaturated fatty acids (ω3-LCPUFA). During the final week, scopolamine induced acute cholinergic dysfunction. Neuroinflammation was assessed in the dentate gyrus by IHC (Iba-1, COX-2, and TNF-α) and by IF of astrocytes (GFAP intensity and morphology). Docking was employed to evaluate interactions of oleic and palmitic acids, EPA, and DHA with AChE, COX-2, BACE1, and TREM2. All HFD groups attenuated scopolamine-induced increases in Iba-1, COX-2 and TNF-α compared with the SD-scopolamine group, with limited separation among lipid classes under this acute stressor. By contrast, astroglial readouts showed a clear hierarchy: EVOO-HFD produced the lowest GFAP signal and the most ramified morphology, followed closely by ω3-LCPUFA, with ROO being intermediate and SFA being the least favourable. Docking supported a mechanistic framework: EPA/DHA displayed stronger predicted engagement than oleate/palmitate at COX-2 and BACE1, while long-chain fatty acids occupied the AChE peripheral site and a lipid/apoE-responsive surface on TREM2. In conclusion, PUFA-rich feeding, and notably that with the EVOO matrix, preferentially buffers hippocampal neuroinflammation in a scopolamine-induced Alzheimer's-like model. These findings support a composition, binding, and function framework and strengthen the translational rationale for precision nutrition strategies prioritizing ω3-LCPUFA and high-quality olive oils. - Source: PubMed
Publication date: 2026/05/14
Albertuni MarluaTorrecillas-Lopez MariaGonzalez-de la Rosa TeresaBarrera-Chamorro LunaMarquez-Paradas ElviraDel Rio-Vazquez Jose LNavarro-Hortal Maria DClaro-Cala Carmen MMontserrat-de la Paz Sergio