ArticleThe Journal of clinical investigation2020
Prion protein glycans reduce intracerebral fibril formation and spongiosis in prion disease.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Distinctive properties of the prion protein in the brain and retina in the amyloidosis associated with the PRNP F198S mutation.Acta neuropathologica · 2026Article
- Distinctive properties of the prion protein in the brain and retina in the amyloidosis associated with the PRNP F198S Mutation.Research square · 2026Article
- The axonal transport velocity of prions is independent of prion formation.PLoS pathogens · 2026Article
- D178N prion protein mutation endows RML prions with new strain properties that do not mimic human genetic prion diseases.Acta neuropathologica · 2026Article
- Genome-wide screens identify core regulators of cell surface prion protein expression.Scientific reports · 2026Article
- The molecular determinants of a universal prion acceptor.PLoS pathogens · 2024Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host.Brain : a journal of neurology · 2024Article
- Review
- Post-translational modifications in prion diseases.Frontiers in molecular neuroscience · 2024Review
- N-glycans show distinct spatial distribution in mouse brain.Glycobiology · 2023Article
- Article
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- Phospholipid cofactor solubilization inhibits formation of native prions.Journal of neurochemistry · 2023Article
- Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection.PLoS pathogens · 2023Article
- A novel subtype of sporadic Creutzfeldt-Jakob disease with PRNP codon 129MM genotype and PrP plaques.Acta neuropathologica · 2023Article
- Thiophene-Based Ligands: Design, Synthesis and Their Utilization for Optical Assignment of Polymorphic-Disease-Associated Protein Aggregates.Chembiochem : a European journal of chemical biology · 2023Review
- N-glycans show distinct spatial distribution in mouse brain.bioRxiv : the preprint server for biology · 2023Article
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Prion assemblies: structural heterogeneity, mechanisms of formation, and role in species barrier.Cell and tissue research · 2023Review
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Posttranslational modifications (PTMs) are common among proteins that aggregate in neurodegenerative disease, yet how PTMs impact the aggregate conformation and disease progression remains unclear. By engineering knockin mice expressing prion protein (PrP) lacking 2 N-linked glycans (Prnp180Q/196Q), we provide evidence that glycans reduce spongiform degeneration and hinder plaque formation in prion disease. Prnp180Q/196Q mice challenged with 2 subfibrillar, non-plaque-forming prion strains instead developed plaques highly enriched in ADAM10-cleaved PrP and heparan sulfate (HS). Intriguingly, a third strain composed of intact, glycophosphatidylinositol-anchored (GPI-anchored) PrP was relatively unchanged, forming diffuse, HS-deficient deposits in both the Prnp180Q/196Q and WT mice, underscoring the pivotal role of the GPI-anchor in driving the aggregate conformation and disease phenotype. Finally, knockin mice expressing triglycosylated PrP (Prnp187N) challenged with a plaque-forming prion strain showed a phenotype reversal, with a striking disease acceleration and switch from plaques to predominantly diffuse, subfibrillar deposits. Our findings suggest that the dominance of subfibrillar aggregates in prion disease is due to the replication of GPI-anchored prions, with fibrillar plaques forming from poorly glycosylated, GPI-anchorless prions that interact with extracellular HS. These studies provide insight into how PTMs impact PrP interactions with polyanionic cofactors, and highlight PTMs as a major force driving the prion disease phenotype.
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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.