ArticleCell death & disease2021
Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Model systems informing mechanisms and drug discovery: a review ofWellcome open research · 2023Pooled it
- Non-Mammalian Models for Mitochondria Research in CNS Disorders.Biomolecules · 2026Review
- Progressive cognitive impairment and ventricular tachycardia in a boy with biallelic POLG variants and a de novo RYR2 variation.Scientific reports · 2026Article
- Model organisms in POLG-related disorders: insights from yeast to multicellular systems.Cell death & disease · 2025Review
- Skeletal Muscle Pathology in Autosomal Recessive Cerebellar Ataxias: Insights from Marinesco-Sjögren Syndrome.International journal of molecular sciences · 2025Review
- POLG p.A962T Mutation Leads to Neuronal Mitochondrial Dysfunction That is Restored After Mitochondrial Transplantation.Physiological research · 2024Article
- Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.Genes · 2024Review
- Review
- Zebrafish polg2 knock-out recapitulates human POLG-disorders; implications for drug treatment.Cell death & disease · 2024Article
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Drug Drop Test: How to Quickly Identify Potential Therapeutic Compounds for Mitochondrial Diseases Using YeastInternational journal of molecular sciences · 2023Review
- Distinct longevity mechanisms across and within species and their association with aging.Cell · 2023Article
- Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays.International journal of molecular sciences · 2023Review
- Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models.International journal of molecular sciences · 2023Review
- DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.Cell & bioscience · 2022Review
- The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases.International journal of molecular sciences · 2022Review
- Hyperactivation of Wnt/β-catenin and Jak/Stat3 pathways in human and zebrafish foetal growth restriction models: Implications for pharmacological rescue.Frontiers in cell and developmental biology · 2022Article
- Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Zebrafish Models of Autosomal Recessive Ataxias.Cells · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA polymerase gamma (Polg) is a nuclear-encoded enzyme involved in DNA replication in animal mitochondria. In humans, mutations in the POLG gene underlie a set of mitochondrial diseases characterized by mitochondrial DNA (mtDNA) depletion or deletion and multiorgan defects, named POLG disorders, for which an effective therapy is still needed. By applying antisense strategies, ENU- and CRISPR/Cas9-based mutagenesis, we have generated embryonic, larval-lethal and adult-viable zebrafish Polg models. Morphological and functional characterizations detected a set of phenotypes remarkably associated to POLG disorders, including cardiac, skeletal muscle, hepatic and gonadal defects, as well as mitochondrial dysfunctions and, notably, a perturbed mitochondria-to-nucleus retrograde signaling (CREB and Hypoxia pathways). Next, taking advantage of preliminary evidence on the candidate molecule Clofilium tosylate (CLO), we tested CLO toxicity and then its efficacy in our zebrafish lines. Interestingly, at well tolerated doses, the CLO drug could successfully rescue mtDNA and Complex I respiratory activity to normal levels, even in mutant phenotypes worsened by treatment with Ethidium Bromide. In addition, the CLO drug could efficiently restore cardio-skeletal parameters and mitochondrial mass back to normal values. Altogether, these evidences point to zebrafish as a valuable vertebrate organism to faithfully phenocopy multiple defects detected in POLG patients. Moreover, this model represents an excellent platform to screen, at the whole-animal level, candidate molecules with therapeutic effects in POLG disorders.
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.