ArticleNature structural & molecular biology2025
Microglia promote inflammatory cell death upon neuronal mitochondrial impairment during neurodegeneration.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Orally activatable membrane fusion-mitochondria hitchhiking on intestinal macrophages for targeted therapy of bacterial meningitis and neuroinflammation.Bioactive materials · 2027Article
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Coordinated transcriptional shifts in microglia and oligodendrocytes from neurodevelopment to inflammaging.npj aging · 2026Article
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- The zinc-nitric oxide axis in acute brain injury: Convergent oxidative-nitrative stress, peroxynitrite signaling, and therapeutic targets.Redox biology · 2026Review
- Nanotechnology-driven STING regulation for on-demand therapy.Acta pharmaceutica Sinica. B · 2026Review
- Article
- PANoptosis and mitochondrial regulatory mechanisms in cerebral ischemia-reperfusion injury.Frontiers in physiology · 2026Review
- Closing 2025, and a look ahead.Nature structural & molecular biology · 2025Article
- The Inflammatory Cell Death in Diabetic Kidney Disease: Integrating Multifactorial Mechanisms into Novel Therapeutics.International journal of molecular sciences · 2025Review
- Aged brain multi-omic integration captures immunometabolic and sex variation.bioRxiv : the preprint server for biology · 2025Article
- Neuronal VPS13D loss drives microglial activation.Nature structural & molecular biology · 2025Article
- Marine Derived Strategies Against Neurodegeneration.Marine drugs · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The failure to clear dysfunctional mitochondria, cell death and inflammation have been linked in neurodegenerative disease, but their relationship and role in these conditions is not fully understood. Loss of Vps13d prevents clearance of mitochondria, and mutations in human VPS13D have been associated with neurological movement disorders. To investigate the relationship between mitochondrial health, inflammation and neurodegeneration, we created a conditional Vps13d-knockout mouse. Loss of Vps13d in excitatory neurons resulted in behavioral changes and neurodegeneration. Vacuolar protein sorting 13D (VPS13D) deficiency also caused mitochondrial ultrastructural defects and dysfunction in neurons followed by gasdermin E processing, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon response cGAMP interactor (STING) signaling, microglial activation and cell death. Gasdermin E localization with mitochondria in Vps13d-mutant neurons was required for elevated extracellular mitochondrial DNA that promoted activation of microglia. Depletion of microglia suppressed cell death and behavioral phenotypes but not mitochondrial changes in the neuron-specific Vps13d-knockout model, indicating that microglia promote cell death in this model of neurodegenerative disease.
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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.