ArticleThe Journal of clinical investigation2016
Astrocytes are central in the pathomechanisms of vanishing white matter.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
93 citing papers in PubMed, 180 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Pediatric pharmacokinetics and pharmacodynamics of guanabenz for the treatment of vanishing white matter.Scientific reports · 2026Article
- Targeting MAPK-dependent pathways to modulate reactive astrocyte pathology in neurodegeneration.Communications biology · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Endogenous Repair in Vanishing White Matter.Annals of neurology · 2026Article
- Article
- Targeting astrocytic CLC2(CLCN2) restores myelin regeneration through inhibition of SPP1/CD44 signaling pathway in leukoencephalopathy.Molecular psychiatry · 2026Article
- Growth Differentiation Factor 15 Elevation in the Central Nervous System Is Associated With Failure to Thrive in Alexander Disease.Annals of clinical and translational neurology · 2026Article
- Prime editing links the split integrated stress response to pathogenic eIF2B mutations and white matter degeneration.Cell death & disease · 2025Article
- Consensus-Based Expert Recommendations for Diagnosis and Clinical Management of Vanishing White Matter.Neurology · 2025Review
- Cell-specific Eif2b5 mutant mice: novel insights into roles of macroglia in vanishing white matter.Brain : a journal of neurology · 2025Article
- Article
- Chronic integrated stress response causes dysregulated cholesterol synthesis in white matter disease.JCI insight · 2025Article
- Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology.Neurobiology of disease · 2025Article
- The translational landscape of reactive astrocytes reveals the impact of eIF2B-mediated dysregulation in VWM disease.NAR molecular medicine · 2025Article
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Aerobic Exercise Improves Cognitive Recovery in Mice with Chronic Cerebral Hypoperfusion by Modulating the Annexin-A1-MAPK Axis and Astrocyte Polarization.Aging and disease · 2024Article
- eIF2B localization and its regulation during the integrated stress response is cell-type specific.iScience · 2024Article
- Article
- Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.Neuroradiology · 2024Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vanishing white matter (VWM) is a fatal leukodystrophy that is caused by mutations in genes encoding subunits of eukaryotic translation initiation factor 2B (eIF2B). Disease onset and severity are codetermined by genotype. White matter astrocytes and oligodendrocytes are almost exclusively affected; however, the mechanisms of VWM development remain unclear. Here, we used VWM mouse models, patients' tissue, and cell cultures to investigate whether astrocytes or oligodendrocytes are the primary affected cell type. We generated 2 mouse models with mutations (Eif2b5Arg191His/Arg191His and Eif2b4Arg484Trp/Arg484Trp) that cause severe VWM in humans and then crossed these strains to develop mice with various mutation combinations. Phenotypic severity was highly variable and dependent on genotype, reproducing the clinical spectrum of human VWM. In all mutant strains, impaired maturation of white matter astrocytes preceded onset and paralleled disease severity and progression. Bergmann glia and retinal Müller cells, nonforebrain astrocytes that have not been associated with VWM, were also affected, and involvement of these cells was confirmed in VWM patients. In coculture, VWM astrocytes secreted factors that inhibited oligodendrocyte maturation, whereas WT astrocytes allowed normal maturation of VWM oligodendrocytes. These studies demonstrate that astrocytes are central in VWM pathomechanisms and constitute potential therapeutic targets. Importantly, astrocytes should also be considered in the pathophysiology of other white matter disorders.
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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.