Characterization of the molecular interaction between α-synuclein and prion protein
| dc.contributor.advisor | Fernández, Claudio | |
| dc.contributor.coadvisor | Outeiro, Tiago F. | |
| dc.creator | Garcia Domingues, Renato | |
| dc.date.accessioned | 2026-04-16T12:06:23Z | |
| dc.date.available | 2026-04-16T12:06:23Z | |
| dc.date.issued | 2023-05-10 | |
| dc.description.abstract | The interaction between α-synuclein (aSyn) and prion protein (PrP) has been implicated in the pathogenesis of synucleinopathies. However, the nature of this interaction remains poorly understood. Here, we employed a combination of bio-physical and cellular assays to characterize the interaction between aSyn and PrP. Our results demonstrate that the C-terminal region of aSyn interacts with PrP in an orientation-specific manner through electrostatic interactions, and suggest that tryptophan residues on PrP may also bind to the tyrosine residues of aSyn through aromatic interactions. We further demonstrate that PrP potentiates seeded aSyn aggregation kinetics, as evidenced by an increase in monomer incorporation rate in the real-time quaking-induced conversion assay. Additionally, we observed colocalization between PrP and phosphorylated aSyn, suggesting a possible role of PrP in aSyn phosphorylation. Our findings provide valuable insights into the nature of the aSyn-PrP interaction and highlight potential therapeutic targets for synucleinopathies. In particular, targeting the C-terminal of aSyn or the N-terminal of PrP could be a promising strategy for preventing or reversing the effects of aSyn aggregation and spreading. Future studies could investigate the role of post-translational modifications of aSyn and the conformational states of aSyn in the interaction with PrP, as well as the effect of aSyn aggregates formed via PrP-aSyn interaction on cellular toxicity and spreading. | |
| dc.description.fil | Fil: Garcia Domingues, Renato. Universidad Nacional de Rosario; Argentina. | |
| dc.identifier.uri | https://hdl.handle.net/2133/32873 | |
| dc.language.iso | en | |
| dc.rights | openAccess | |
| dc.rights.holder | Garcia Domingues, Renato | |
| dc.rights.text | Attribution-NonCommercial-ShareAlike 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
| dc.subject | Neurodegeneration | |
| dc.subject | NMR | |
| dc.subject | Synuclein | |
| dc.subject | Protein-protein interaction | |
| dc.subject | synucleinopathies | |
| dc.subject | Parkinson’s disease | |
| dc.title | Characterization of the molecular interaction between α-synuclein and prion protein | |
| dc.type | tesis | |
| dc.type.collection | tesis | |
| dc.type.other | tesis de doctorado | |
| dc.type.version | publishedVersion |