ArticleThe EMBO journal2015
Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: a new mechanism for ALS.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04840823 (A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin), which is not on this map. Cited by 132 papers, 2 of them syntheses that pooled it.
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.
A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin (200mg Twice Daily, 400mg Twice Daily and 600mg Twice Daily) in Adults With Amyotrophic Lateral Sclerosis
Who cites it
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.
- TDP-43 related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review and narrative synthesis.Frontiers in molecular neuroscience · 2026Pooled it
- The Role of MicroRNAs in Patients with Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2018Pooled it
- NurOwn, phase 2, randomized, clinical trial in patients with ALS: Safety, clinical, and biomarker results.Neurology · 2019Trial
- Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.Molecular therapy. Advances · 2026Article
- Canonical microRNA loss drives tumor development, implicating therapeutic efficacy of enoxacin in angiosarcoma.RNA (New York, N.Y.) · 2026Article
- Harnessing machine learning models to repurpose drugs targeting HIV-1 integrase, protease, and reverse transcriptase.Scientific reports · 2026Article
- Preservation of miR-9-5p and miR-124-3p in ALS-resistant oculomotor neurons contrasts with their downregulation in vulnerable spinal motor neurons, irrespective of TDP-43 pathology.Acta neuropathologica · 2026Article
- Modulation of the miR-485-3p/PGC-1α Pathway by ASO-Loaded Nanoparticles Attenuates ALS Pathogenesis.International journal of molecular sciences · 2026Article
- Benchmarking pre-trained genomic language models for RNA sequence-related predictive applications.Nature communications · 2025Article
- IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication.medRxiv : the preprint server for health sciences · 2025Article
- miR-146a is a Pleiotropic Regulator of Motor Neuron Degeneration.bioRxiv : the preprint server for biology · 2025Article
- Article
- Canonical microRNA loss drives tumor development implicating therapeutic efficacy of enoxacin in angiosarcoma.bioRxiv : the preprint server for biology · 2025Article
- Dicer Is Involved in Cytotoxicity and Motor Impairment Induced by TBPH Deficiency.Current issues in molecular biology · 2025Article
- A cell type-specific expression atlas of small and total RNA in the heart after myocardial infarction.Scientific data · 2025Article
- Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2025Review
- Serum/glucose starvation enhances binding of miR-4745-5p and miR-6798-5p toNon-coding RNA research · 2025Article
- Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs.Pharmaceutics · 2025Article
- Hsa-miR-532-3p protects human decidual mesenchymal stem cells from oxidative stress in recurrent spontaneous abortion via targeting KEAP1.Redox biology · 2025Article
- Traffic light at DSB-transit regulation between gene transcription and DNA repair.FEBS letters · 2025Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Interest in RNA dysfunction in amyotrophic lateral sclerosis (ALS) recently aroused upon discovering causative mutations in RNA-binding protein genes. Here, we show that extensive down-regulation of miRNA levels is a common molecular denominator for multiple forms of human ALS. We further demonstrate that pathogenic ALS-causing mutations are sufficient to inhibit miRNA biogenesis at the Dicing step. Abnormalities of the stress response are involved in the pathogenesis of neurodegeneration, including ALS. Accordingly, we describe a novel mechanism for modulating microRNA biogenesis under stress, involving stress granule formation and re-organization of DICER and AGO2 protein interactions with their partners. In line with this observation, enhancing DICER activity by a small molecule, enoxacin, is beneficial for neuromuscular function in two independent ALS mouse models. Characterizing miRNA biogenesis downstream of the stress response ties seemingly disparate pathways in neurodegeneration and further suggests that DICER and miRNAs affect neuronal integrity and are possible therapeutic targets.
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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.