Gast ::
| Hauptseite > Publikationsdatenbank > Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide |
| Hauptseite > Publikationsdatenbank > Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide |
| Journal Article | FZJ-2025-03861 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2025
Springer Nature
[London]
This record in other databases: 
Please use a persistent id in citations: doi:10.1038/s41531-025-01132-7 doi:10.34734/FZJ-2025-03861
Abstract: 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.
; 
; 
; 
; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
PDF