ArticleProceedings of the National Academy of Sciences of the United States of America2021
Unfolded and intermediate states of PrP play a key role in the mechanism of action of an antiprion chaperone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Systematic review of pharmacological management in Creutzfeldt-Jakob disease: no options so far?Arquivos de neuro-psiquiatria · 2022Pooled it
- 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
- A review on current theories and potential therapies for prion diseases.Molecular biology reports · 2025Review
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- FAIR data for optical tweezers experiments.Biophysical journal · 2025Review
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- Single-molecule magnetic tweezers to probe the equilibrium dynamics of individual proteins at physiologically relevant forces and timescales.Nature protocols · 2024Review
- Accurate Memory Kernel Extraction from Discretized Time-Series Data.Journal of chemical theory and computation · 2024Article
- Article
- Article
- A tetracationic porphyrin with dual anti-prion activity.iScience · 2023Article
- Altered properties of amyloidogenic prion protein in genetic Creutzfeldt-Jakob disease with PRNP V180I mutation in response to pentosan polysulfate.Brain pathology (Zurich, Switzerland) · 2023Article
- Prion therapeutics: Lessons from the past.Prion · 2022Review
- One-step asparaginyl endopeptidase (RSC chemical biology · 2022Article
- Article
- Pentosan polysulfate induces low-level persistent prion infection keeping measurable seeding activity without PrP-res detection in Fukuoka-1 infected cell cultures.Scientific reports · 2022Article
- Highly Dynamic Polynuclear Metal Cluster Revealed in a Single Metallothionein Molecule.Research (Washington, D.C.) · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prion and prion-like diseases involve the propagation of misfolded protein conformers. Small-molecule pharmacological chaperones can inhibit propagated misfolding, but how they interact with disease-related proteins to prevent misfolding is often unclear. We investigated how pentosan polysulfate (PPS), a polyanion with antiprion activity in vitro and in vivo, interacts with mammalian prion protein (PrP) to alter its folding. Calorimetry showed that PPS binds two sites on natively folded PrP, but one PPS molecule can bind multiple PrP molecules. Force spectroscopy measurements of single PrP molecules showed PPS stabilizes not only the native fold of PrP but also many different partially folded intermediates that are not observed in the absence of PPS. PPS also bound tightly to unfolded segments of PrP, delaying refolding. These observations imply that PPS can act through multiple possible modes, inhibiting misfolding not only by stabilizing the native fold or sequestering natively folded PrP into aggregates, as proposed previously, but also by binding to partially or fully unfolded states that play key roles in mediating misfolding. These results underline the likely importance of unfolded states as critical intermediates on the prion conversion pathway.
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