ArticleNeuron2016
Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2α Signaling as a Generalizable Mechanism for Dystonia.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 54 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.
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.
Brain Networks in Dystonia
Imaging Genetics of Laryngeal Dystonia
Who cites it
54 citing papers in PubMed, 88 citations in OpenAlex.
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Response to GPi-DBS in a Case of EIF2AK2-Associated Early-Onset Generalized Dystonia.Movement disorders clinical practice · 2026Article
- Article
- Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.Biochemical Society transactions · 2025Review
- Striatal cell-type-specific molecular signatures reveal potential therapeutic targets in a model of dystonia.Neurobiology of disease · 2025Article
- Neurobiology of Dystonia: Review of Genetics, Animal Models, and Neuroimaging.Brain sciences · 2025Review
- Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Mutation in Prkra results in cerebellar abnormality and reduced eIF2α phosphorylation in a model of DYT-PRKRA.Disease models & mechanisms · 2024Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- Blood-Based Proteomics for Adult-Onset Focal Dystonias.Annals of neurology · 2024Article
- A frameshift mutation in the murinebioRxiv : the preprint server for biology · 2024Article
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- RANBP17 Overexpression Restores Nucleocytoplasmic Transport and Ameliorates Neurodevelopment in Induced DYT1 Dystonia Motor Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- DYT-THAP1: exploring gene expression in fibroblasts for potential biomarker discovery.Neurogenetics · 2024Article
- The integrated stress response pathway and neuromodulator signaling in the brain: lessons learned from dystonia.The Journal of clinical investigation · 2024Review
- Macro- and micro-structural insights into primary dystonia: a UK Biobank study.Journal of neurology · 2024Article
- DYT-Frontiers in neuroscience · 2023Review
- DYT-TOR1A genotype alters extracellular vesicle composition in murine cell model and shows potential for biomarker discovery.Dystonia (Lausanne, Switzerland) · 2023Article
- Attenuation of Piwil2 induced by hypoxic postconditioning prevents cerebral ischemic injury by inhibiting CREB2 promoter methylation.Brain pathology (Zurich, Switzerland) · 2023Article
- Synaptic Dysfunction in Dystonia: Update From Experimental Models.Current neuropharmacology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 1 country.
Funding
Abstract
Dystonia is a brain disorder causing involuntary, often painful movements. Apart from a role for dopamine deficiency in some forms, the cellular mechanisms underlying most dystonias are currently unknown. Here, we discover a role for deficient eIF2α signaling in DYT1 dystonia, a rare inherited generalized form, through a genome-wide RNAi screen. Subsequent experiments including patient-derived cells and a mouse model support both a pathogenic role and therapeutic potential for eIF2α pathway perturbations. We further find genetic and functional evidence supporting similar pathway impairment in patients with sporadic cervical dystonia, due to rare coding variation in the eIF2α effector ATF4. Considering also that another dystonia, DYT16, involves a gene upstream of the eIF2α pathway, these results mechanistically link multiple forms of dystonia and put forth a new overall cellular mechanism for dystonia pathogenesis, impairment of eIF2α signaling, a pathway known for its roles in cellular stress responses and synaptic plasticity.
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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.