ArticleProceedings of the National Academy of Sciences of the United States of America2009
Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 144 citations in OpenAlex.
- Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding.Prion · 2026Article
- Red ginseng-mediated modulation of the NLRP3 Inflammasome in neuroinflammatory-related cognitive impairments.Journal of ginseng research · 2026Review
- Fast and slow strains of misfolded mutant superoxide dismutase 1 in familial amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1Experimental neurology · 2025Article
- Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard.Developmental cell · 2024Article
- Role of NLRP3 inflammasome in central nervous system diseases.Cell & bioscience · 2024Review
- Multiple Factors Influence the Incubation Period of ALS Prion-like Transmission in SOD1 Transgenic Mice.Viruses · 2023Article
- Artificial Hsp104-mediated systems for re-localizing protein aggregates.Nature communications · 2023Article
- Polyglutamylation: biology and analysis.Amino acids · 2022Review
- Phenotypic diversity in ALS and the role of poly-conformational protein misfolding.Acta neuropathologica · 2021Review
- Variation in the vulnerability of mice expressing human superoxide dismutase 1 to prion-like seeding: a study of the influence of primary amino acid sequence.Acta neuropathologica communications · 2021Article
- MARK2 phosphorylates eIF2α in response to proteotoxic stress.PLoS biology · 2021Article
- Age-dependent degeneration of an identified adult leg motor neuron in aBiology open · 2020Article
- Trifluoroethanol Partially Unfolds G93A SOD1 Leading to Protein Aggregation: A Study by Native Mass Spectrometry and FPOP Protein Footprinting.Biochemistry · 2020Article
- Molecular and pharmacological chaperones for SOD1.Biochemical Society transactions · 2020Review
- POSCAbilities: The Application of the Prion Organotypic Slice Culture Assay to Neurodegenerative Disease Research.Biomolecules · 2020Review
- Functional diversity between HSP70 paralogs caused by variable interactions with specific co-chaperones.The Journal of biological chemistry · 2020Article
- Nucleation and kinetics of SOD1 aggregation in human cells for ALS1.Molecular and cellular biochemistry · 2020Article
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
Recent studies suggest that superoxide dismutase 1 (SOD1)-linked amyotrophic lateral sclerosis results from destabilization and misfolding of mutant forms of this abundant cytosolic enzyme. Here, we have tracked the expression and fate of a misfolding-prone human SOD1, G85R, fused to YFP, in a line of transgenic G85R SOD1-YFP mice. These mice, but not wild-type human SOD1-YFP transgenics, developed lethal paralyzing motor symptoms at 9 months. In situ RNA hybridization of spinal cords revealed predominant expression in motor neurons in spinal cord gray matter in all transgenic animals. Concordantly, G85R SOD-YFP was diffusely fluorescent in motor neurons of animals at 1 and 6 months of age, but at the time of symptoms, punctate aggregates were observed in cell bodies and processes. Biochemical analyses of spinal cord soluble extracts indicated that G85R SOD-YFP behaved as a misfolded monomer at all ages. It became progressively insoluble at 6 and 9 months of age, associated with presence of soluble oligomers observable by gel filtration. Immunoaffinity capture and mass spectrometry revealed association of G85R SOD-YFP, but not WT SOD-YFP, with the cytosolic chaperone Hsc70 at all ages. In addition, 3 Hsp110's, nucleotide exchange factors for Hsp70s, were captured at 6 and 9 months. Despite such chaperone interactions, G85R SOD-YFP formed insoluble inclusions at late times, containing predominantly intermediate filament proteins. We conclude that motor neurons, initially "compensated" to maintain the misfolded protein in a soluble state, become progressively unable to do so.
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