ArticleeLife2023
TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed.
- CXCL10 contributes to female-specific pathological progression in tauopathy model mice.Journal of neuroinflammation · 2026Article
- RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.Journal of neuroinflammation · 2026Review
- Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.Journal of extracellular vesicles · 2026Article
- Modular inflammation network discovery from large-scale phenotypic screening in genetically heterogeneous mouse brains.Journal of neuroinflammation · 2025Article
- Alternating hemiplegia of childhood associated mutations in Atp1a3 reveal diverse neurological alterations in mice.Neurobiology of disease · 2025Article
- TPL2 kinase activity is required forFrontiers in immunology · 2025Article
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Article
- Revealing key role of T cells in neurodegenerative diseases, with potential to develop new targeted therapies.Translational neuroscience · 2023Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor progression locus 2 (TPL2) (MAP3K8) is a central signaling node in the inflammatory response of peripheral immune cells. We find that TPL2 kinase activity modulates microglial cytokine release and is required for microglia-mediated neuron death in vitro. In acute in vivo neuroinflammation settings, TPL2 kinase activity regulates microglia activation states and brain cytokine levels. In a tauopathy model of chronic neurodegeneration, loss of TPL2 kinase activity reduces neuroinflammation and rescues synapse loss, brain volume loss, and behavioral deficits. Single-cell RNA sequencing analysis indicates that protection in the tauopathy model was associated with reductions in activated microglia subpopulations as well as infiltrating peripheral immune cells. Overall, using various models, we find that TPL2 kinase activity can promote multiple harmful consequences of microglial activation in the brain including cytokine release, iNOS (inducible nitric oxide synthase) induction, astrocyte activation, and immune cell infiltration. Consequently, inhibiting TPL2 kinase activity could represent a potential therapeutic strategy in neurodegenerative conditions.
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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.