Dokument: Mechanistic insights into α-synuclein aggregation: from fibril stability to surface nucleation
| Titel: | Mechanistic insights into α-synuclein aggregation: from fibril stability to surface nucleation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=51832 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20191219-115144-2 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | M.Sc. Peduzzo, Alessia [Autor] | |||||||
| Dateien: |
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| Beitragende: | Jun.-Prof. Büll, Alexander [Gutachter] Jun.-Prof. Strodel, Birgit [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | α-synuclein(α-syn) is a natively unfolded protein, which can aggregate into amyloid fibrils, the major hallmark of Parkinson's disease (PD). PD is the second most common neurodegenerative disease; in fact it has been estimated that in 2040 14.2 million people will be affected by PD worldwide. Therefore a better understanding of the aggregation mechanisms of α-syn and its link with the disease is necessary for combatting it.
In Chapter 3, the thermal and chemical stability of α-syn fibrils has been investigated. It is demonstrated that α-syn fibrils can denature when they are incubated for prolonged time at 4 °C. Moreover, it is discussed that this process is arising from a decrease in the strength of hydrophobic interactions. Hydrophobic interactions are the major stability factor for amyloid fibrils, hence a weakening of these interactions renders it plausible that amyloid fibrils can cold-denature, as also folded proteins. In Chapter 4, the nucleation of α-syn on fibril surfaces has been investigated. This type of nucleation process has only been recognised to play an important role in amyloid fibril formation in the last decade. There are several important open questions in relation to this process. Here I have addressed the question concerning the ability of surface nucleation to propagate properties of the seed fibrils. It has been demonstrated that secondary nucleation of α-syn amyloid fibrils does not propagate the fibril structure and rather resembles a generic heterogeneous nucleation process. Due to the generic nature of this process, it can also occur in the presence of fibrils formed by another protein, such as β-syn. In Chapter 5 is shown how lipid-bilayer nanodiscs composed by α-syn as scaffold protein constitutes a reproducible tool to investigate the aggregation of α-syn upon binding to lipids. Taken together, this thesis establishes important new insights into both the stability of α-syn fibrils, as well as their process of formation on the surface of other fibrils. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 19.12.2019 | |||||||
| Dateien geändert am: | 19.12.2019 | |||||||
| Promotionsantrag am: | 22.10.2019 | |||||||
| Datum der Promotion: | 11.11.2019 |
