ArticleActa neuropathologica2016
Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 148 citations in OpenAlex.
- Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding.Prion · 2026Article
- Seeds from ALS patients homozygous for the SOD1 D90A mutation transmit two types of SOD1 aggregation and motor neuron disease.Acta neuropathologica · 2026Article
- The axonal transport velocity of prions is independent of prion formation.PLoS pathogens · 2026Article
- A phase I study to evaluate the dosimetry and safety of [European journal of nuclear medicine and molecular imaging · 2026Article
- Nose-to-brain delivery of a SOD1-stabilizing small molecule ameliorates pathology in an ALS mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Scalable assay to identify inhibitors of prion-like propagation of protein misfolding as potential therapeutics for neurodegeneration.Protein science : a publication of the Protein Society · 2026Article
- Fast and slow strains of misfolded mutant superoxide dismutase 1 in familial amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- Neurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment.International journal of molecular sciences · 2025Review
- Landscapes of missense variant impact for human superoxide dismutase 1.American journal of human genetics · 2025Article
- Diverse effects of coexpression of human SOD1 variants on motor neuron disease.Human molecular genetics · 2025Article
- Impact of SOD1 Transcript Variants on Amyotrophic Lateral Sclerosis Severity.International journal of molecular sciences · 2025Article
- SOD1 Protein Content in Human Central Nervous System and Peripheral Tissues.Journal of neurochemistry · 2025Article
- Antibody-Based PET Imaging of Misfolded Superoxide Dismutase 1 in an Amyotrophic Lateral Sclerosis Mouse Model.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins.Molecular and cellular biology · 2025Article
- The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.Brain communications · 2025Review
- Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.Science advances · 2024Article
- Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy.Nature communications · 2024Article
- Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.Molecular neurodegeneration · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A hallmark feature of amyotrophic lateral sclerosis (ALS) is that symptoms appear to spread along neuroanatomical pathways to engulf the motor nervous system, suggesting a propagative toxic entity could be involved in disease pathogenesis. Evidence for such a propagative entity emerged recently in studies using mice that express G85R-SOD1 mutant protein fused to YFP (G85R-SOD1:YFP). Heterozygous G85R-SOD1:YFP transgenic mice do not develop ALS symptoms out to 20 months of age. However, when newborns are injected with spinal homogenates from paralyzed mutant SOD1 mice, the G85R-SOD1:YFP mice develop paralysis as early as 6 months of age. We now demonstrate that injecting spinal homogenates from paralyzed mutant SOD1 mice into the sciatic nerves of adult G85R-SOD1:YFP mice produces a spreading motor neuron disease within 3.0 ± 0.2 months of injection. The formation of G85R-SOD1:YFP inclusion pathology spreads slowly in this model system; first appearing in the ipsilateral DRG, then lumbar spinal cord, before spreading rostrally up to the cervical cord by the time mice develop paralysis. Reactive astrogliosis mirrors the spread of inclusion pathology and motor neuron loss is most severe in lumbar cord. G85R-SOD1:YFP inclusion pathology quickly spreads to discrete neurons in the brainstem and midbrain that are synaptically connected to spinal neurons, suggesting a trans-synaptic propagation of misfolded protein. Taken together, the data presented here describe the first animal model that recapitulates the spreading phenotype observed in patients with ALS, and implicates the propagation of misfolded protein as a potential mechanism for the spreading of motor neuron disease.
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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.