ArticleThe Journal of clinical investigation2015
NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05537220 (NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients With Retinitis Pigmentosa), which is not on this map. Cited by 172 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.
NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients With Retinitis Pigmentosa
Who cites it
172 citing papers in PubMed, 279 citations in OpenAlex.
- Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial.The Journal of clinical investigation · 2020Trial
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Experimental upregulation of Lancl1 promotes axon regeneration after optic nerve injury in vivo.Experimental neurology · 2026Article
- The Role of Nrf2 in SIRT1-Mediated RGC Neuroprotection in Traumatic Optic Neuropathy.Translational vision science & technology · 2026Article
- Advanced glycation end-products exacerbate myocardial ischemia/reperfusion injury by promoting mitochondrial oxidative damage and PANoptosis in diabetes mellitus.Redox biology · 2026Article
- Sigma1 Receptor Activation Confers Durable Neuroprotection Following Neonatal Ischemic Retinal Injury.Research square · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Dual role of microglia in glaucoma: Regulation of neuroinflammation and neuroregeneration.Neural regeneration research · 2026Article
- Nrf2 regulates ICAM-1-mediated neutrophil extracellular trap formation after traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Nrf2 activator peptide protects the brain from cerebral vascular dysfunction in alcohol ingestion.JCI insight · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- Combined Expression of hRdCVF and hRdCVFL Through AAV-Mediated Delivery for the Treatment of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Standardized Hydroxytyrosol-Enriched Olive Pomace Juice Modulates Metabolic and Neurotrophic Signaling Pathways to Attenuate Neuroinflammation and Protect Neuronal Cells.Molecules (Basel, Switzerland) · 2026Article
- Epigallocatechin gallate in N-methyl-N-nitrosourea-induced retinitis pigmentosa mouse model.International journal of ophthalmology · 2026Article
- Exploring the Mechanism of 2,4-Dichlorophenoxyacetic Acid in Causing Neurodegenerative Diseases Based on Network Toxicology and Molecular Docking.International journal of molecular sciences · 2025Article
- Reactive Oxygen Species Regulation Across Retinitis Pigmentosa Animal Models: A 25-Year Systematized Review.Molecular neurobiology · 2025Review
- Neuron-Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury.Antioxidants (Basel, Switzerland) · 2025Review
- Fermented Soybean Pulp Alleviates Disease Progression of 5×FAD Model Mice.Molecular neurobiology · 2025Article
112 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress contributes to the loss of neurons in many disease conditions as well as during normal aging; however, small-molecule agents that reduce oxidation have not been successful in preventing neurodegeneration. Moreover, even if an efficacious systemic reduction of reactive oxygen and/or nitrogen species (ROS/NOS) could be achieved, detrimental side effects are likely, as these molecules regulate normal physiological processes. A more effective and targeted approach might be to augment the endogenous antioxidant defense mechanism only in the cells that suffer from oxidation. Here, we created several adeno-associated virus (AAV) vectors to deliver genes that combat oxidation. These vectors encode the transcription factors NRF2 and/or PGC1a, which regulate hundreds of genes that combat oxidation and other forms of stress, or enzymes such as superoxide dismutase 2 (SOD2) and catalase, which directly detoxify ROS. We tested the effectiveness of this approach in 3 models of photoreceptor degeneration and in a nerve crush model. AAV-mediated delivery of NRF2 was more effective than SOD2 and catalase, while expression of PGC1a accelerated photoreceptor death. Since the NRF2-mediated neuroprotective effects extended to photoreceptors and retinal ganglion cells, which are 2 very different types of neurons, these results suggest that this targeted approach may be broadly applicable to many diseases in which cells suffer from oxidative damage.
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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.