Dokument: Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide
| Titel: | Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=71268 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20251107-114317-0 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Sevenich, Marc [Autor] Kass, Bettina [Autor] Kupreichyk, Tatsiana [Autor] Pauly, Thomas [Autor] Stoldt, Matthias [Autor] Hoyer, Wolfgang [Autor] Lakomek, Nils-Alexander [Autor] Nagel-Steger, Luitgard [Autor] Gremer, Lothar [Autor] Tamgüney, Gültekin [Autor] | |||||||
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| Beschreibung: | A hallmark of Parkinson’s disease (PD) is the progressive neurodegeneration associated with soluble oligomeric and fibrillar forms of misfolded α-synuclein (α-syn). In this study, all-d-enantiomeric peptide ligands are presented that bind monomeric α-syn with high affinity, stabilize its physiological monomeric status, prevent aggregation and dissolve existing aggregates. This “antiprionic” mode of action directly targets pathogenic aggregated particles. Using mirror-image phage display on d-enantiomeric full-length α-syn, SVD-1 and SVD-1a were identified, showing a delay of aggregation and reduction of aggregate formation in both de novo and seeded models. Picomolar KDs were confirmed by SPR, where a highly dynamic interaction mode was verified by PRE-NMR. SVD-1a also reduced the toxicity and intracellular seeding of α-syn fibrils in cell culture by disassembling them into monomers, as confirmed by atomic force microscopy and dynamic light scattering. These results support SVD-1a as a promising lead compound for the treatment of Parkinson’s disease. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Sevenich, M., Gering, I., Kass, B., Vollmer, M., Aghabashlou Saisan, S., Tusche, M., Kupreichyk, T., Pauly, T., Stoldt, M., Hoyer, W., Willuweit, A., Kutzsche, J., Lakomek, N.-A., Nagel-Steger, L., Gremer, L., Tamgüney, G. E., Mohrlüder, J., & Willbold, D. (2025). Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide. Npj Parkinson’s Disease, 11, Article 271. https://doi.org/10.1038/s41531-025-01132-7 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 07.11.2025 | |||||||
| Dateien geändert am: | 07.11.2025 |
