ArticleProceedings of the National Academy of Sciences of the United States of America2013
C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02869048 (Amyotrophic Lateral Sclerosis and the Innate Immune System), which is not on this map. Cited by 47 papers, 2 of them syntheses that pooled it.
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.
Amyotrophic Lateral Sclerosis and the Innate Immune System
Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Meta-analysis of transcriptomic changes in optic nerve injury and neurodegenerative models reveals a fundamental response to injury throughout the central nervous system.Molecular vision · 2017Pooled it
- Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.JAMA neurology · 2023Trial
- The Gut Microbiome in Amyotrophic Lateral Sclerosis: Emerging Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- Neurovascular dysfunction in the development and progression of neuroinflammatory diseases.Frontiers in cellular neuroscience · 2026Review
- Review
- Functional significance of commonly regulated genes in mechanically and chemically induced retinal ganglion cell death in rat eyes.Scientific reports · 2025Article
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- Synapse Regulation.Advances in neurobiology · 2024Review
- Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation.Nature communications · 2023Article
- Differential regulation of microglial states by colony stimulating factors.Frontiers in cellular neuroscience · 2023Review
- C1q and central nervous system disorders.Frontiers in immunology · 2023Review
- Microglia in motor neuron disease: Signaling evidence from last 10 years.Developmental neurobiology · 2022Review
- The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration.Biomolecules · 2022Review
- New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022.Frontiers in pharmacology · 2022Review
- C-Boutons and Their Influence on Amyotrophic Lateral Sclerosis Disease Progression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Aberrant Complement System Activation in Neurological Disorders.International journal of molecular sciences · 2021Review
- The Benefits of Complement Measurements for the Clinical Practice.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Bone Marrow Stromal Cell Antigen 2: Is a Potential Neuroinflammation Biomarker of SOD1Frontiers in neuroscience · 2021Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Accumulating evidence from mice expressing ALS-causing mutations in superoxide dismutase (SOD1) has implicated pathological immune responses in motor neuron degeneration. This includes microglial activation, lymphocyte infiltration, and the induction of C1q, the initiating component of the classic complement system that is the protein-based arm of the innate immune response, in motor neurons of multiple ALS mouse models expressing dismutase active or inactive SOD1 mutants. Robust induction early in disease course is now identified for multiple complement components (including C1q, C4, and C3) in spinal cords of SOD1 mutant-expressing mice, consistent with initial intraneuronal C1q induction, followed by global activation of the complement pathway. We now test if this activation is a mechanistic contributor to disease. Deletion of the C1q gene in mice expressing an ALS-causing mutant in SOD1 to eliminate C1q induction, and complement cascade activation that follows from it, is demonstrated to produce changes in microglial morphology accompanied by enhanced loss, not retention, of synaptic densities during disease. C1q-dependent synaptic loss is shown to be especially prominent for cholinergic C-bouton nerve terminal input onto motor neurons in affected C1q-deleted SOD1 mutant mice. Nevertheless, overall onset and progression of disease are unaffected in C1q- and C3-deleted ALS mice, thus establishing that C1q induction and classic or alternative complement pathway activation do not contribute significantly to SOD1 mutant-mediated ALS pathogenesis in mice.
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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.