The role of triggering receptor expressed on myeloid cells-1 (TREM-1) in central nervous system diseases

Kan, Xugang; Zhang, Baole; Ni, Haibo; Shao, Jianfeng

doi:10.1186/s13041-022-00969-w

Cited by 18 publications

(14 citation statements)

References 138 publications

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“…Of potential relevance to age-related loss of motor synapses, the translatomes of both aged female and male motor neurons are enriched for genes with roles in the complement system and TREM1 signaling ( Figure 8H ). Both complement signaling ( 62 – 66 ) and TREM1 ( 67 , 68 ) have been shown to mediate synaptic pruning by microglia; thus, motor neurons undergo molecular changes during aging that may cause microglia to target motor synapses.…”

Section: Resultsmentioning

confidence: 99%

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Castro¹,

Lopes²,

Settlage³

et al. 2023

JCI Insight

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Spinal motor neurons have been implicated in the loss of motor function that occurs with advancing age. However, the cellular and molecular mechanisms that impair the function of these neurons during aging remain unknown. Here, we show that motor neurons do not die in old female and male mice, rhesus monkeys, and humans. Instead, these neurons selectively and progressively shed excitatory synaptic inputs throughout the soma and dendritic arbor during aging. Thus, aged motor neurons contain a motor circuitry with a reduced ratio of excitatory to inhibitory synapses that may be responsible for the diminished ability to activate motor neurons to commence movements. An examination of the motor neuron translatome (ribosomal transcripts) in male and female mice reveals genes and molecular pathways with roles in glia-mediated synaptic pruning, inflammation, axonal regeneration, and oxidative stress that are upregulated in aged motor neurons. Some of these genes and pathways are also found altered in motor neurons affected with amyotrophic lateral sclerosis (ALS) and responding to axotomy, demonstrating that aged motor neurons are under significant stress. Our findings show mechanisms altered in aged motor neurons that could serve as therapeutic targets to preserve motor function during aging.

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Section: Resultsmentioning

confidence: 99%

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Castro¹,

Lopes²,

Settlage³

et al. 2023

JCI Insight

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“…mTREM-1 is a type I transmembrane glycoprotein receptor composed of an extracellular immunoglobulin domain, a transmembrane region, and a cytoplasmic domain ( 49 ). The extracellular domain is primarily responsible for ligand binding, while the transmembrane region associates with the DNAX-activating protein 12 (DAP12) adapter protein through non-covalent bonds, transmitting signals within the cell ( 50 ). sTREM-1 is a glycosylated peptide with only one immunoglobulin-like domain.…”

Section: Overview Of the Trem Familymentioning

confidence: 99%

“…Little is known about the ligands that activate TREM1. Limited evidence suggested that high mobility group box 1 (HMGB1), PGN recognition protein 1 (PGLYRP1), heat shock protein 70 (HSP70), CD177, actin, and extracellular cold-inducible RNA-binding protein (eCIRP) may be ligands for TREM-1 ( 50 , 54 , 55 ).…”

Section: Overview Of the Trem Familymentioning

confidence: 99%

“…Therefore, sTREM-1 can be used as an inflammatory biomarker to assess the severity of ICH and predict early neurological function deterioration ( 62 ). TREM1 is primarily expressed in microglia/macrophages within the central nervous system ( 50 ). TREM-1 and HMGB1 expression increased after ICH, and the two proteins interacted to promote an inflammatory response.…”

Section: The Role Of Trem1 In Hemorrhagic Strokementioning

confidence: 99%

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Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications

Kong,

Wang,

Jin

et al. 2024

Front. Neurol.

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Stroke has long been a major threat to human health worldwide. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, exhibits a high incidence rate and a high mortality and disability rate, imposing a substantial burden on both public health and the economy and society. In recent years, the triggering receptor expressed on myeloid cells (TREM) family has garnered extensive attention in various pathological conditions, including hemorrhagic stroke. This review comprehensively summarizes the structure and function of TREM1/2, as well as their roles and potential mechanisms in hemorrhagic stroke, with the aim of providing guidance for the development of targeted therapeutic strategies in the future.

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“…Macrophages are important immune cells in the body and play a key role in chronic inflammation in many lung diseases ( 9 ). Triggering receptor expressed on myeloid cells-1 (TREM-1), a member of the immunoglobulin superfamily, is largely enriched on the surface of myeloid cells including macrophages, monocytes, and neutrophils ( 10 ). A prior study illustrated that TREM-1 stimulated lung injury and inflammation in COPD mouse by mediating macrophage pyroptosis ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m⁶A Methylation

Wang,

Yu,

Xiao

et al. 2024

Immune Netw

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Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro , exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo , mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68 + cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO −CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

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The role of triggering receptor expressed on myeloid cells-1 (TREM-1) in central nervous system diseases

Cited by 18 publications

References 138 publications

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m⁶A Methylation

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The role of triggering receptor expressed on myeloid cells-1 (TREM-1) in central nervous system diseases

Cited by 18 publications

References 138 publications

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates, and humans

Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

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Resources

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Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m⁶A Methylation