Validation of Poly(Propylene Imine) Glycodendrimers Towards Their Anti-prion Conversion Efficiency
| Autor: | Dimitra Dafou, Matthias Schmitz, Theodoros Sklaviadis, Inga Zerr, Dietmar Appelhans, Anna Villar-Piqué, Katrin Thüne, Eirini Kanata, Niccolò Candelise, Susana Margarida da Silva Correia, Franc Llorens |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Dendrimers Glycosylation Prions animal diseases Neuroscience (miscellaneous) Polypropylenes chemistry [Polypropylenes] Creutzfeldt-Jakob Syndrome 03 medical and health sciences Cellular and Molecular Neuroscience Protein Aggregates 0302 clinical medicine pathology [Brain] ddc:570 Cell Line Tumor Humans metabolism [Fluorescein-5-isothiocyanate] Prion protein Propylene imine Chemistry Brain Reproducibility of Results cerebrospinal fluid [Creutzfeldt-Jakob Syndrome] nervous system diseases 030104 developmental biology Neurology Biochemistry metabolism [Prions] chemistry [Dendrimers] Fluorescein-5-isothiocyanate 030217 neurology & neurosurgery |
| Zdroj: | Molecular neurobiology 57(4), 1863-1874 (2019). doi:10.1007/s12035-019-01837-w |
| DOI: | 10.1007/s12035-019-01837-w |
| Popis: | Prion diseases, such as the sporadic Creutzfeldt-Jakob disease (sCJD), are a class of fatal neurodegenerative disorders. Currently, there is no efficient treatment or therapy available. Hence, the search for molecules that may inhibit the conversion of the cellular prion protein (PrPC) into its pathological counterpart PrPScrapie (PrPSc) is of great urgency. Here, we report the generation- and dose-dependent biological action of dense-shell poly(propylene imine) (PPI) glycodendrimers by using scrapie-infected neuroblastoma (ScN2a) cells and the real-time quaking-induced conversion assay (RT-QuIC) for validation of anti-prion efficiencies. Whereas the 2nd and 3rd generation of PPI glycodendrimers exhibited anti-prion conversion efficiency in ScN2a cells validated by RT-QuIC analysis, we observed that the 4th generation of glycodendrimers had shown no significant effect. Translational RT-QuIC studies conducted with human prions derived from sCJD patients indicated an anti-prion conversion effect (not on PrPRes degradation) of PPI glycodendrimers against human prions with the highest inhibitory activity of the 4th generation of PPI glycodendrimers towards prion aggregation compared to the 2nd and 3rd generation. In conclusion, our study highlights the potential of PPI glycodendrimers as therapeutic compounds due to their anti-conversion activity on human prions in a PrPSc strain depending manner. |
| Databáze: | OpenAIRE |
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