ArticleMolecular neurodegeneration2011
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 100 citations in OpenAlex.
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- Induction of endogenous IL-10 promotes resolution and tolerance of nitric oxide in microglia.Brain, behavior, & immunity - health · 2025Article
- Localization and Pathological Implications of Lipopolysaccharide in the Brains of 5XFAD Mice.Molecular neurobiology · 2025Article
- Lipopolysaccharide and Recombinant Prion Protein Induce Distinct Neurodegenerative Pathologies in FVB/N Mice.International journal of molecular sciences · 2025Article
- Regulation of Nrf2/GPX4 Signaling Pathway by Hyperbaric Oxygen Protects Against Depressive Behavior and Cognitive Impairment in a Spinal Cord Injury Rat Model.CNS neuroscience & therapeutics · 2025Article
- p38α Mitogen-Activated Protein Kinase-An Emerging Drug Target for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Review
- Article
- Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).International journal of molecular medicine · 2023Review
- Tolerized Microglia Protect Neurons Against Endotoxin-Induced TNF-α Production via an LBP-Dependent Intracellular p38 MAPK Signaling Pathway.Inflammation · 2023Article
- The Involvement of Neuroinflammation in the Onset and Progression of Parkinson's Disease.International journal of molecular sciences · 2023Review
- Review
- Development of Novel Herbal Compound Formulations Targeting Neuroinflammation: Network Pharmacology, Molecular Docking, and Experimental Verification.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Role of chemokine-like factor 1 as an inflammatory marker in diseases.Frontiers in immunology · 2023Review
- Neuronal chemokine-like-factor 1 (CKLF1) up-regulation promotes M1 polarization of microglia in rat brain after stroke.Acta pharmacologica Sinica · 2022Article
- Essential Oils fromAntioxidants (Basel, Switzerland) · 2021Article
- Gram-negative bacteria and their lipopolysaccharides in Alzheimer's disease: pathologic roles and therapeutic implications.Translational neurodegeneration · 2021Review
- Roles and Interaction of the MAPK Signaling Cascade in Aβ25-35-Induced Neurotoxicity Using an Isolated Primary Hippocampal Cell Culture System.Cellular and molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.
resultsWe found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory cytokine TNFα was demonstrated by the findings that p38α KO microglia produced much less TNFα in response to LPS compared to WT microglia, that adding back TNFα to KO microglia/neuron co-cultures increased the LPS-induced neuron damage, and that neutralization of TNFα in WT microglia/neuron co-cultures prevented the neuron damage. These results using cell-selective, isoform-specific KO mice demonstrate that the p38α MAPK isoform in microglia is a key mediator of LPS-induced neuronal and synaptic dysfunction. The findings also provide evidence that a major mechanism by which LPS activation of microglia p38α MAPK signaling leads to neuron damage is through up-regulation of the proinflammatory cytokine TNFα.
conclusionsThe data suggest that selective targeting of p38α MAPK signaling should be explored as a potential therapeutic strategy for CNS disorders where overproduction of proinflammatory cytokines is implicated in disease progression.
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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.