ArticleThe Journal of biological chemistry2011
Alsin and SOD1(G93A) proteins regulate endosomal reactive oxygen species production by glial cells and proinflammatory pathways responsible for neurotoxicity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review.Advances in therapy · 2020Pooled it
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.Neurobiology of disease · 2026Article
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Superoxide dismutase and neurological disorders.IBRO neuroscience reports · 2024Review
- Intrathecal delivery of AAV-NDNF ameliorates disease progression of ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.Frontiers in pharmacology · 2022Review
- NOX2 Activation in COVID-19: Possible Implications for Neurodegenerative Diseases.Medicina (Kaunas, Lithuania) · 2021Review
- Intersection between Redox Homeostasis and Autophagy: Valuable Insights into Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- When It Comes to an End: Oxidative Stress Crosstalk with Protein Aggregation and Neuroinflammation Induce Neurodegeneration.Antioxidants (Basel, Switzerland) · 2020Review
- Mitigation of ALS Pathology by Neuron-Specific Inhibition of Nuclear Factor Kappa B Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Dysregulation of Rac or Rho elicits death of motor neurons and activation of these GTPases is altered in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis.Neurobiology of disease · 2020Article
- Emerging Evidence Highlighting the Importance of Redox Dysregulation in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS).Frontiers in cellular neuroscience · 2020Article
- Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review.Frontiers in physiology · 2020Review
- Amyloid-beta impairs TOM1-mediated IL-1R1 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Peroxynitrite Activates the NLRP3 Inflammasome Cascade in SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2018Article
- Aged Mouse Cortical Microglia Display an Activation Profile Suggesting Immunotolerogenic Functions.International journal of molecular sciences · 2018Article
- Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4Frontiers in cellular neuroscience · 2018Review
- Glial responses during epileptogenesis in Mus musculus point to potential therapeutic targets.PloS one · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent studies have implicated enhanced Nox2-mediated reactive oxygen species (ROS) by microglia in the pathogenesis of motor neuron death observed in familial amyotrophic lateral sclerosis (ALS). In this context, ALS mutant forms of SOD1 enhance Rac1 activation, leading to increased Nox2-dependent microglial ROS production and neuron cell death in mice. It remains unclear if other genetic mutations that cause ALS also function through similar Nox-dependent pathways to enhance ROS-mediate motor neuron death. In the present study, we sought to understand whether alsin, which is mutated in an inherited juvenile form of ALS, functionally converges on Rac1-dependent pathways acted upon by SOD1(G93A) to regulate Nox-dependent ROS production. Our studies demonstrate that glial cell expression of SOD1(G93A) or wild type alsin induces ROS production, Rac1 activation, secretion of TNFα, and activation of NFκB, leading to decreased motor neuron survival in co-culture. Interestingly, coexpression of alsin, or shRNA against Nox2, with SOD1(G93A) in glial cells attenuated these proinflammatory indicators and protected motor neurons in co-culture, although shRNAs against Nox1 and Nox4 had little effect. SOD1(G93A) expression dramatically enhanced TNFα-mediated endosomal ROS in glial cells in a Rac1-dependent manner and alsin overexpression inhibited SOD1(G93A)-induced endosomal ROS and Rac1 activation. SOD1(G93A) expression enhanced recruitment of alsin to the endomembrane compartment in glial cells, suggesting that these two proteins act to modulate Nox2-dependent endosomal ROS and proinflammatory signals that modulate NFκB. These studies suggest that glial proinflammatory signals regulated by endosomal ROS are influenced by two gene products known to cause ALS.
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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.