ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Idebenone Has Distinct Effects on Mitochondrial Respiration in Cortical Astrocytes Compared to Cortical Neurons Due to Differential NQO1 Activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Idebenone does not inhibit disability progression in primary progressive MS.Multiple sclerosis and related disorders · 2020Trial
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Amyloid precursor protein interacts with the mitochondrial phosphatase PGAM5 and regulates mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Strategic Targeting of Mitochondria: Bridging Biology and Therapy for Health Benefits.Cell biochemistry and biophysics · 2026Review
- Review
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Comparative Antioxidant Protection of Cochlear Hair Cells from Ototoxins.Molecules (Basel, Switzerland) · 2025Article
- Evaluation of Visual and Optical Coherence Tomography Outcomes in Patients with Leber's Hereditary Optic Neuropathy Treated with Idebenone.Life (Basel, Switzerland) · 2025Article
- Article
- Idebenone Enhances the Early Microglial Response to Traumatic Brain Injury and Mitigates Acute Gene Expression Changes to Ephrin-A and Dopamine Signaling Pathways.bioRxiv : the preprint server for biology · 2025Article
- Review
- Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.Cell reports. Medicine · 2024Article
- Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.Cell reports. Medicine · 2024Article
- Modification of Preservative Fluids with Antioxidants in Terms of Their Efficacy in Liver Protection before Transplantation.International journal of molecular sciences · 2024Review
- Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.Neurotoxicity research · 2023Review
- Anti-inflammatory reprogramming of microglia cells by metabolic modulators to counteract neurodegeneration; a new role for Ranolazine.Scientific reports · 2023Article
- Clinical Approaches for Mitochondrial Diseases.Cells · 2023Review
- Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules · 2023Review
- Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber's Hereditary Opic Neuropathy.International journal of molecular sciences · 2022Review
- Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation.Antioxidants (Basel, Switzerland) · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Idebenone is a synthetic quinone that on reduction in cells can bypass mitochondrial Complex I defects by donating electrons to Complex III. The drug is used clinically to treat the Complex I disease Leber's hereditary optic neuropathy (LHON), but has been less successful in clinical trials for other neurodegenerative diseases. NAD(P)H:quinone oxidoreductase 1 (NQO1) appears to be the main intracellular enzyme catalyzing idebenone reduction. However, NQO1 is not universally expressed by cells of the brain. Using primary rat cortical cells pooled from both sexes, we tested the hypotheses that the level of endogenous NQO1 activity limits the ability of neurons, but not astrocytes, to use idebenone as an electron donor to support mitochondrial respiration. We then tested the prediction that NQO1 induction by pharmacological activation of the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) enables idebenone to bypass Complex I in cells with poor NQO1 expression. We found that idebenone stimulated respiration by astrocytes but reduced the respiratory capacity of neurons. Importantly, idebenone supported mitochondrial oxygen consumption in the presence of a Complex I inhibitor in astrocytes but not neurons, and this ability was reversed by inhibiting NQO1. Conversely, recombinant NQO1 delivery to neurons prevented respiratory impairment and conferred Complex I bypass activity. Nrf2 activators failed to increase NQO1 in neurons, but carnosic acid induced NQO1 in COS-7 cells that expressed little endogenous enzyme. Carnosic acid-idebenone combination treatment promoted NQO1-dependent Complex I bypass activity in these cells. Thus, combination drug strategies targeting NQO1 may promote the repurposing of idebenone for additional disorders.
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Registered trials
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