ArticleNature2015
A naturally occurring variant of the human prion protein completely prevents prion disease.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- The first meta-analysis of the G96S single nucleotide polymorphism (SNP) of the prion protein gene (Frontiers in veterinary science · 2024Pooled it
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.Neurobiology of disease · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.PLoS pathogens · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.bioRxiv : the preprint server for biology · 2026Article
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.bioRxiv : the preprint server for biology · 2026Article
- Assessment of the biochemical basis underlying the resistance against systemic amyloidosis.Scientific reports · 2026Article
- Membrane-anchored PrPSc is the trigger for prion synaptotoxicity.PLoS pathogens · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions.Frontiers in neuroscience · 2026Review
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Review
- Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Evolution of Experimental Rodent Models for Prion Diseases.Journal of neurochemistry · 2025Review
- Isolation of a novel human prion strain from a PRNP codon 129 heterozygous vCJD patient.PLoS pathogens · 2025Article
- Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals.Biomedicines · 2024Article
- Exonuclease-enhanced prime editors.Nature methods · 2024Article
- Review
- A structural basis for prion strain diversity.Nature chemical biology · 2023Article
- A single protective polymorphism in the prion protein blocks cross-species prion replication in cultured cells.Journal of neurochemistry · 2023Article
- Organoids for modeling prion diseases.Cell and tissue research · 2023Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.
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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.