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Exploring Methods for Fast Discrimination of α-Synuclein Fibril Polymorphs

Os, O.J.D. van (2025) Exploring Methods for Fast Discrimination of α-Synuclein Fibril Polymorphs.

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Abstract:Pathologies associated with α-synuclein aggregation are often referred to as synucleinopathies. While each synucleinopathy requires disease specific treatment, diagnosis is challenging since patients share common symptoms. Therefore, a fast and reliable discrimination of α-synuclein fibril polymorphs is clinically highly desirable. In this thesis, several polymorph discrimination methods are explored, mainly targeting the fuzzy coat of fibrils through a gel electrophoresis-based proteinase K digestion assay. Gel electrophoresis data was successfully quantified by constructing intensity profiles (IPs) from gel images. From these IPs, polymorph specific Proteinase K digestion sites were discovered for A53T and E46K point mutated strains that aggregated in high salt (HS) and low salt (LS) conditions. For the WT strain, only Proteinase K characteristic digestion sites were established for fibrils that aggregated in HS conditions, since aggregation in LS conditions yielded too few fibrils to be investigated. The results of this thesis lay the foundation for promising, novel and fast α-synuclein fibril polymorph discrimination methods, having the potential to enhance the diagnosis and targeted treatment of synucleinopathies.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:35 chemistry, 42 biology
Programme:Biomedical Engineering MSc (66226)
Link to this item:https://purl.utwente.nl/essays/107953
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