ArticleThe Journal of clinical investigation2022
JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Integrative Transcriptomics Identifies Ubiquitination-Related GenesJournal of inflammation research · 2026Article
- Neutrophil membrane-camouflaged SiRNA nanoplatform targeting IL-33 attenuates osteoarthritis through autophagy-dependent senescence regulation.Journal of nanobiotechnology · 2025Article
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- Article
- Association of Functional Gene Variants in DYSF-ZNF638, MTSS1 and Ferroptosis-Related Genes with Multiple Sclerosis Severity and Target Gene Expression.International journal of molecular sciences · 2025Article
- Senescent cell reduction does not improve recovery in mice under experimental autoimmune encephalomyelitis (EAE) induced demyelination.Journal of neuroinflammation · 2025Article
- Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases.Stem cell research & therapy · 2025Review
- Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain.Neurobiology of aging · 2024Article
- Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease.Communications biology · 2024Article
- Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.Translational neurodegeneration · 2024Review
- The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model.Cellular and molecular life sciences : CMLS · 2023Article
- Regulatory mechanisms and therapeutic potential of JAB1 in neurological development and disorders.Molecular medicine (Cambridge, Mass.) · 2023Review
- NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss.Molecular neurodegeneration · 2023Article
- Evaluation of Oxidative Stress and Metabolic Profile in a Preclinical Kidney Transplantation Model According to Different Preservation Modalities.International journal of molecular sciences · 2023Article
- Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer.Heliyon · 2022Article
- Lifespan and ROS levels in different Drosophila melanogaster strains after 24 h hypoxia exposure.Biology open · 2022Article
- [Exosomes derived from mesenchymal stem cells alleviate white matter damage in neonatal rats by targeting the NLRP3 inflammasome].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsArticle
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation, and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target.
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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 Socratic graph.