ArticleCell death & disease2015
Induction of COX-2-PGE2 synthesis by activation of the MAPK/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
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- A Sleeping Opportunity Does Not Restore Hippocampal Alterations Induced by 10 Days of Sleep Restriction in Rats.Neurochemical research · 2025Article
- Natural Hydroxybenzoic and Hydroxycinnamic Acids Derivatives: Mechanisms of Action and Therapeutic Applications.Antioxidants (Basel, Switzerland) · 2025Review
- A zinc transporter drives glioblastoma progression via extracellular vesicles-reprogrammed microglial plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Acid-sensing ion channel-1 contributes to the failure of myelin sheath regeneration following spinal cord injury by transcellular delivery of PGE2.Cellular & molecular biology letters · 2024Article
- The murine metastatic microenvironment of experimental brain metastases of breast cancer differs by host age in vivo: a proteomic study.Clinical & experimental metastasis · 2024Article
- ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.Acta pharmaceutica Sinica. B · 2024Article
- Deficient chaperone-mediated autophagy facilitates LPS-induced microglial activation via regulation of the p300/NF-κB/NLRP3 pathway.Science advances · 2023Article
- Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation.Acta pharmacologica Sinica · 2023Article
- UBQLN2 and HSP70 participate in Parkin-mediated mitophagy by facilitating outer mitochondrial membrane rupture.EMBO reports · 2023Article
- Inhibition of the MEK/ERK pathway suppresses immune overactivation and mitigates TDP-43 toxicity in a Drosophila model of ALS.Immunity & ageing : I & A · 2023Article
- Update on the pathological roles of prostaglandin ETranslational neurodegeneration · 2023Review
- The neuroprotective effects of peracetylated chitosan oligosaccharides against β-amyloid-induced cognitive deficits in rats.Marine life science & technology · 2023Article
- Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity.Translational neurodegeneration · 2022Review
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
- MiR-30a-5p and miR-153-3p regulate LPS-induced neuroinflammatory response and neuronal apoptosis by targeting NeuroD1.BMB reports · 2022Article
- Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation is a striking hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Previous studies have shown the contribution of glial cells such as astrocytes in TDP-43-linked ALS. However, the role of microglia in TDP-43-mediated motor neuron degeneration remains poorly understood. In this study, we show that depletion of TDP-43 in microglia, but not in astrocytes, strikingly upregulates cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production through the activation of MAPK/ERK signaling and initiates neurotoxicity. Moreover, we find that administration of celecoxib, a specific COX-2 inhibitor, greatly diminishes the neurotoxicity triggered by TDP-43-depleted microglia. Taken together, our results reveal a previously unrecognized non-cell-autonomous mechanism in TDP-43-mediated neurodegeneration, identifying COX-2-PGE2 as the molecular events of microglia- but not astrocyte-initiated neurotoxicity and identifying celecoxib as a novel potential therapy for TDP-43-linked ALS and possibly other types of ALS.
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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.