ArticleNeurobiology of disease2015
Highly specific ubiquitin-competing molecules effectively promote frataxin accumulation and partially rescue the aconitase defect in Friedreich ataxia cells.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- The Regulation of the Disease-Causing GeneCells · 2024Review
- Interferon Gamma Enhances Cytoprotective Pathways via Nrf2 and MnSOD Induction in Friedreich's Ataxia Cells.International journal of molecular sciences · 2023Article
- Dimorphic frataxin and its gene regulation by sex steroids in hamsters.Molecular genetics and genomics : MGG · 2023Article
- Article
- Mitochondrial biology and dysfunction in secondary mitochondrial disease.Open biology · 2022Review
- Posttranslational regulation of mitochondrial frataxin and identification of compounds that increase frataxin levels in Friedreich's ataxia.The Journal of biological chemistry · 2022Article
- Drug Repositioning in Friedreich Ataxia.Frontiers in neuroscience · 2022Review
- Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich's Ataxia Patients.International journal of molecular sciences · 2020Article
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- The Cardioprotective Mechanism of Phenylaminoethyl Selenides (PAESe) Against Doxorubicin-Induced Cardiotoxicity Involves Frataxin.Frontiers in pharmacology · 2020Article
- SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia.Nucleic acids research · 2019Article
- Molecular Mechanisms and Therapeutics for the GAA·TTC Expansion Disease Friedreich Ataxia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Transcriptional profiling of isogenic Friedreich ataxia neurons and effect of an HDAC inhibitor on disease signatures.The Journal of biological chemistry · 2019Article
- Increased Frataxin Expression Induced in Friedreich Ataxia Cells by Platinum TALE-VP64s or Platinum TALE-SunTag.Molecular therapy. Nucleic acids · 2018Article
- Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model.Disease models & mechanisms · 2018Article
- Plasma Markers of Neurodegeneration Are Raised in Friedreich's Ataxia.Frontiers in cellular neuroscience · 2018Article
- In Silico Studies in Drug Research Against Neurodegenerative Diseases.Current neuropharmacology · 2018Review
- Article
- E3 Ligase RNF126 Directly Ubiquitinates Frataxin, Promoting Its Degradation: Identification of a Potential Therapeutic Target for Friedreich Ataxia.Cell reports · 2017Article
- Friedreich Ataxia: current status and future prospects.Cerebellum & ataxias · 2017Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Friedreich ataxia is an inherited neurodegenerative disease that leads to progressive disability. There is currently no effective treatment and patients die prematurely. The underlying genetic defect leads to reduced expression of the mitochondrial protein frataxin. Frataxin insufficiency causes mitochondrial dysfunction and ultimately cell death, particularly in peripheral sensory ganglia. There is an inverse correlation between the amount of residual frataxin and the severity of disease progression; therefore, therapeutic approaches aiming at increasing frataxin levels are expected to improve patients' conditions. We previously discovered that a significant amount of frataxin precursor is degraded by the ubiquitin/proteasome system before its functional mitochondrial maturation. We also provided evidence for the therapeutic potential of small molecules that increase frataxin levels by docking on the frataxin ubiquitination site, thus preventing frataxin ubiquitination and degradation. We called these compounds ubiquitin-competing molecules (UCM). By extending our search for effective UCM, we identified a set of new and more potent compounds that more efficiently promote frataxin accumulation. Here we show that these compounds directly interact with frataxin and prevent its ubiquitination. Interestingly, these UCM are not effective on the ubiquitin-resistant frataxin mutant, indicating their specific action on preventing frataxin ubiquitination. Most importantly, these compounds are able to promote frataxin accumulation and aconitase rescue in cells derived from patients, strongly supporting their therapeutic potential.
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