Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity
Amyloid aggregation, including aggregation and propagation of prion protein, is a key factor in numerous human diseases, so-called amyloidosis, with a very poor ability for treatment or prevention. The present work describes the effect of sulfated or sulfonated polymers (sodium dextran sulfate, poly...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/14/7/1478 |
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| author | Pavel Semenyuk Diana Evstafyeva Vladimir Izumrudov Vladimir Muronetz |
| author_facet | Pavel Semenyuk Diana Evstafyeva Vladimir Izumrudov Vladimir Muronetz |
| author_sort | Pavel Semenyuk |
| collection | DOAJ |
| description | Amyloid aggregation, including aggregation and propagation of prion protein, is a key factor in numerous human diseases, so-called amyloidosis, with a very poor ability for treatment or prevention. The present work describes the effect of sulfated or sulfonated polymers (sodium dextran sulfate, polystyrene sulfonate, polyanethole sulfonate, and polyvinyl sulfate) on different stages of amyloidogenic conversion and aggregation of the prion protein, which is associated with prionopathies in humans and animals. All tested polymers turned out to induce amyloid conversion of the ovine prion protein. As suggested from molecular dynamics simulations, this effect probably arises from destabilization of the native prion protein structure by the polymers. Short polymers enhanced its further aggregation, whereas addition of high-molecular poly(styrene sulfonate) inhibited amyloid fibrils formation. According to the seeding experiments, the protein–polymer complexes formed after incubation with poly(styrene sulfonate) exhibited significantly lower amyloidogenic capacity compared with the control fibrils of the free prion protein. The cytotoxicity of soluble oligomers was completely inhibited by treatment with poly(styrene sulfonate). To summarize, sulfonated polymers are a promising platform for the formulation of a new class of anti-prion and anti-amyloidosis therapeutics. |
| first_indexed | 2024-03-09T11:29:15Z |
| format | Article |
| id | doaj.art-24a5a964115e43ecb7507b82418be8e5 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T11:29:15Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-24a5a964115e43ecb7507b82418be8e52023-11-30T23:55:00ZengMDPI AGPolymers2073-43602022-04-01147147810.3390/polym14071478Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its ToxicityPavel Semenyuk0Diana Evstafyeva1Vladimir Izumrudov2Vladimir Muronetz3Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119234 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaAmyloid aggregation, including aggregation and propagation of prion protein, is a key factor in numerous human diseases, so-called amyloidosis, with a very poor ability for treatment or prevention. The present work describes the effect of sulfated or sulfonated polymers (sodium dextran sulfate, polystyrene sulfonate, polyanethole sulfonate, and polyvinyl sulfate) on different stages of amyloidogenic conversion and aggregation of the prion protein, which is associated with prionopathies in humans and animals. All tested polymers turned out to induce amyloid conversion of the ovine prion protein. As suggested from molecular dynamics simulations, this effect probably arises from destabilization of the native prion protein structure by the polymers. Short polymers enhanced its further aggregation, whereas addition of high-molecular poly(styrene sulfonate) inhibited amyloid fibrils formation. According to the seeding experiments, the protein–polymer complexes formed after incubation with poly(styrene sulfonate) exhibited significantly lower amyloidogenic capacity compared with the control fibrils of the free prion protein. The cytotoxicity of soluble oligomers was completely inhibited by treatment with poly(styrene sulfonate). To summarize, sulfonated polymers are a promising platform for the formulation of a new class of anti-prion and anti-amyloidosis therapeutics.https://www.mdpi.com/2073-4360/14/7/1478prion proteinamyloidpolyanionamyloidosisartificial chaperonepolystyrene sulfonate |
| spellingShingle | Pavel Semenyuk Diana Evstafyeva Vladimir Izumrudov Vladimir Muronetz Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity Polymers prion protein amyloid polyanion amyloidosis artificial chaperone polystyrene sulfonate |
| title | Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity |
| title_full | Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity |
| title_fullStr | Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity |
| title_full_unstemmed | Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity |
| title_short | Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity |
| title_sort | synthetic sulfated polymers control amyloid aggregation of ovine prion protein and decrease its toxicity |
| topic | prion protein amyloid polyanion amyloidosis artificial chaperone polystyrene sulfonate |
| url | https://www.mdpi.com/2073-4360/14/7/1478 |
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