ArticleThe Journal of clinical investigation2008
SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.
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Who cites it
200 citing papers in PubMed, 345 citations in OpenAlex.
- Fatty Acid Profile and Antioxidant Status Fingerprint in Sarcopenic Elderly Patients: Role of Diet and Exercise.Nutrients · 2019Trial
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Overcoming Oxidative Stress in Parkinson's Disease: NADPH Oxidase 4 (NOX4) as a Potential Therapeutic Target.Antioxidants (Basel, Switzerland) · 2026Review
- Linking Superoxide Production and Scavenging in Plant Development.Plant, cell & environment · 2026Review
- Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- Skeletal muscle innervation: Reactive oxygen species as regulators of neuromuscular junction dynamics and motor unit remodeling.Free radical biology & medicine · 2025Review
- Impact of cysteine mutations on the structural dynamics and functional impairment of SOD1: insights into the pathogenicity of amyotrophic lateral sclerosis.Genomics & informatics · 2025Article
- Antioxidative Function of Zinc and Its Protection Against the Onset and Progression of Kidney Disease Due to Cadmium.Biomolecules · 2025Review
- Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.International journal of molecular sciences · 2024Article
- The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis.Heliyon · 2024Review
- Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2024Review
- Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters.Biomolecules · 2024Review
- New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis.ACS central science · 2024Article
- Exploring antioxidant strategies in the pathogenesis of ALS.Open life sciences · 2024Review
- NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders.Progress in neurobiology · 2023Review
- Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.Antioxidants (Basel, Switzerland) · 2023Review
140 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegeneration in familial amyotrophic lateral sclerosis (ALS) is associated with enhanced redox stress caused by dominant mutations in superoxide dismutase-1 (SOD1). SOD1 is a cytosolic enzyme that facilitates the conversion of superoxide (O(2)(*-)) to H(2)O(2). Here we demonstrate that SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase-dependent (Nox-dependent) O(2)(*-) production by binding Rac1 and inhibiting its GTPase activity. Oxidation of Rac1 by H(2)O(2) uncoupled SOD1 binding in a reversible fashion, producing a self-regulating redox sensor for Nox-derived O(2)(*-) production. This process of redox-sensitive uncoupling of SOD1 from Rac1 was defective in SOD1 ALS mutants, leading to enhanced Rac1/Nox activation in transgenic mouse tissues and cell lines expressing ALS SOD1 mutants. Glial cell toxicity associated with expression of SOD1 mutants in culture was significantly attenuated by treatment with the Nox inhibitor apocynin. Treatment of ALS mice with apocynin also significantly increased their average life span. This redox sensor mechanism may explain the gain-of-function seen with certain SOD1 mutations associated with ALS and defines new therapeutic targets.
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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.