Groot, Jens de (2023) Modelling the mediation of treatment effects on prion fibril aggregation by intrinsic fibril breakage parameters. Master's Research Project 1, Biology.
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Abstract
Protein aggregation is a key phenomenon in neurodegenerative diseases. Since decades, researchers attempted to capture the dynamics of prion protein propagation with mathematical models. Key mechanisms of protein propagation are elongation of misfolded protein aggregates by the recruitment of monomers and, accordingly, breakage into daughter filaments that can elongate again. It is especially these breakage mechanisms that are important to model. An increasing body of research shows that the breakage rate of linear protein aggregates follows a non-linear relationship with fibril length. Next, it is proposed that the breakage rate depends on the position along which a fibril breaks. Furthermore, there are several treatment options that can be incorporated into a mathematical model, such as chaperones and interferons. The combination of these is important, because different breakage mechanisms may modulate the effect of treatments in different ways. The current study tries to separately implement both length and position-dependent breakage parameters combined with chaperones or interferons as treatment options into a predictive model. We find that a moderate length-dependent breakage or breakage at the center contributes most to measures of (pathogenic) protein fibril propagation. The results are discussed in light of empirical results and clinical practice.
| Item Type: | Thesis (Master's Research Project 1) |
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| Supervisor name: | Doorn, G.S. van |
| Degree programme: | Biology |
| Thesis type: | Master's Research Project 1 |
| Language: | English |
| Date Deposited: | 01 Nov 2023 10:01 |
| Last Modified: | 01 Nov 2023 10:01 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/31576 |
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