ArticlePLoS pathogens2018
A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.Stem cell reports · 2024Article
- Convergent generation of atypical prions in knockin mouse models of genetic prion disease.The Journal of clinical investigation · 2024Article
- Sigma Receptor Ligands Are Potent Antiprion Compounds that Act Independently of Sigma Receptor Binding.ACS chemical neuroscience · 2024Article
- Susceptibility of Beavers to Chronic Wasting Disease.Biology · 2022Article
- Prion protein with a mutant N-terminal octarepeat region undergoes cobalamin-dependent assembly into high-molecular weight complexes.The Journal of biological chemistry · 2022Article
- Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity.International journal of molecular sciences · 2021Review
- Quaternary Structure Changes for PrPMolecular neurobiology · 2021Article
- A seven-residue deletion in PrP leads to generation of a spontaneous prion formed from C-terminal C1 fragment of PrP.The Journal of biological chemistry · 2020Article
- Mutations in Prion Protein Gene: Pathogenic Mechanisms in C-Terminal vs. N-Terminal Domain, a Review.International journal of molecular sciences · 2019Review
- Gerstmann-Sträussler-Scheinker disease revisited: accumulation of covalently-linked multimers of internal prion protein fragments.Acta neuropathologica communications · 2019Article
- Recent advances in the histo-molecular pathology of human prion disease.Brain pathology (Zurich, Switzerland) · 2019Review
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.
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