ArticleRNA (New York, N.Y.)2018
Article in RNA (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Astrocytes in Neurodegeneration: Spatial States, Crosstalk, and Emerging Therapies.Molecular neurobiology · 2026Review
- Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease.The Journal of clinical investigation · 2026Article
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Ribosome association inhibits stress-induced gene mRNA localization to stress granules.Genes & development · 2025Article
- A rare case of adult-onset vanishing white matter leukoencephalopathy with movement disorder, expressing homozygous EIF2B3 and PRKN pathogenic variants.BMC neurology · 2025Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- Evaluation of safety and early efficacy of AAV gene therapy in mouse models of vanishing white matter disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Cell death or survival: Insights into the role of mRNA translational control.Seminars in cell & developmental biology · 2024Review
- Article
- Translation dysregulation in neurodegenerative diseases: a focus on ALS.Molecular neurodegeneration · 2023Review
- Mechanisms underlying phenotypic variation in neurogenetic disorders.Nature reviews. Neurology · 2023Review
- Claudin-11 in health and disease: implications for myelin disorders, hearing, and fertility.Frontiers in cellular neuroscience · 2023Review
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
- Conformational rearrangements upon start codon recognition in human 48S translation initiation complex.Nucleic acids research · 2022Article
- Review
- Measuring Bulk Translation Activity in Single Mammalian Cells During the Integrated Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Oligodendrocytes depend on MCL-1 to prevent spontaneous apoptosis and white matter degeneration.Cell death & disease · 2021Article
- Translational control in aging and neurodegeneration.Wiley interdisciplinary reviews. RNA · 2021Review
- Correlation Between Genotype and Age of Onset in Leukoencephalopathy With Vanishing White Matter.Frontiers in genetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in eIF2B genes cause vanishing white matter disease (VWMD), a fatal leukodystrophy that can manifest following physical trauma or illness, conditions that activate the integrated stress response (ISR). EIF2B is the guanine exchange factor for eIF2, facilitating ternary complex formation and translation initiation. During the ISR, eIF2α is phosphorylated and inhibits eIF2B, causing global translation suppression and stress-induced gene translation, allowing stress adaptation and recovery. We demonstrate that VWMD patient cells hypersuppress translation during the ISR caused by acute ER stress, delaying stress-induced gene expression and interrupting a negative feedback loop that allows translational recovery by GADD34-mediated dephosphorylation of phospho-eIF2α. Thus, cells from VWMD patients undergo a prolonged state of translational hyperrepression and fail to recover from stress. We demonstrate that small molecules targeting eIF2B or the eIF2α kinase PERK rescue translation defects in patient cells. Therefore, defects in the ISR could contribute to white matter loss in VWMD.
Indexed as
Identifiers
What OpenQuestion holds
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.