ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Impaired extracellular secretion of mutant superoxide dismutase 1 associates with neurotoxicity in familial amyotrophic lateral sclerosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 192 citations in OpenAlex.
- Effects of Cyanidin Derivatives for the Aggregation of Cu/Zn Superoxide Dismutase 1.ACS omega · 2026Article
- ABCA1 Transporter Is Involved in the Secretion of CuZn Superoxide Dismutase (SOD)-1 by Activated Human T Lymphocytes.Antioxidants (Basel, Switzerland) · 2025Article
- Development of a targeted BioPROTAC degrader selective for misfolded SOD1.Nature communications · 2025Article
- Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells.Open biology · 2024Article
- Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation.Cytotherapy · 2024Article
- Hepatoprotective Mechanisms Induced by Spinach Methanolic Extract in Rats with Hyperglycemia-An Immunohistochemical Analysis.Antioxidants (Basel, Switzerland) · 2023Article
- Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.Antioxidants (Basel, Switzerland) · 2023Review
- SRF deletion results in earlier disease onset in a mouse model of amyotrophic lateral sclerosis.JCI insight · 2023Article
- Extracellular Vesicles in Amyotrophic Lateral Sclerosis.Life (Basel, Switzerland) · 2022Review
- P2X7 receptor activation mediates superoxide dismutase 1 (SOD1) release from murine NSC-34 motor neurons.Purinergic signalling · 2022Article
- Sequence grammar underlying the unfolding and phase separation of globular proteins.Molecular cell · 2022Article
- NaCell communication and signaling : CCS · 2022Article
- Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis.The EMBO journal · 2021Review
- A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells.International journal of molecular sciences · 2021Article
- Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS.Acta neuropathologica communications · 2021Article
- The Transcriptional Complex Sp1/KMT2A by Up-Regulating Restrictive Element 1 Silencing Transcription Factor Accelerates Methylmercury-Induced Cell Death in Motor Neuron-Like NSC34 Cells Overexpressing SOD1-G93A.Frontiers in neuroscience · 2021Article
- Mutant Cu/Zn Superoxide Dismutase (A4V) Turnover Is Altered in Cells Containing Inclusions.Frontiers in molecular neuroscience · 2021Article
- Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracellular disposal of protein aggregates.Acta neuropathologica · 2020Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the intracellular metalloenzyme superoxide dismutase 1 (SOD1) are linked to neurotoxicity in familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism. Golgi fragmentation and endoplasmic reticulum stress are early hallmarks of spinal motor neuron pathology in transgenic mice overexpressing mutant SOD1, suggesting that dysfunction of the neuronal secretory pathway may contribute to ALS pathogenesis. We therefore proposed that mutant SOD1 directly engages and modulates the secretory pathway based on recent evidence of SOD1 secretion in diverse human cell lines. Here, we demonstrate that a fraction of active endogenous SOD1 is secreted by NSC-34 motor neuron-like cells via a brefeldin-A (BFA)-sensitive pathway. Expression of enhanced green fluorescent protein-tagged mutant human SOD1 (hSOD1-EGFP) in NSC-34 cells induced frequent cytoplasmic inclusions and protein insolubility that correlated with toxicity. In contrast, transfection of non-neuronal COS-7 cells resulted in mutant hSOD1-EGFP cytoplasmic inclusions, oligomerization, and fragmentation without detectable toxicity. Importantly, impaired secretion of hSOD1-EGFP was common to all 10 SOD1 mutants tested relative to wild-type protein in NSC-34 cells. Treatment with BFA inhibited hSOD1-EGFP secretion with pronounced BFA-induced toxicity in mutant cells. Extracellular targeting of mutant hSOD1-EGFP via SOD3 signal peptide fusion attenuated cytoplasmic inclusion formation and toxicity. The effect of elevated extracellular SOD1 was then evaluated in a transgenic rat model of ALS. Chronic intraspinal infusion of exogenous wild-type hSOD1 significantly delayed disease progression and endpoint in transgenic SOD1(G93A) rats. Collectively, these results suggest novel extracellular roles for SOD1 in ALS and support a causal relationship between mutant SOD1 secretion and intraneuronal toxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.