Molecular interactions and aggregation of the huntingtin protein

Schaus, Céline (2020) Molecular interactions and aggregation of the huntingtin protein. --Choose an option--, Sciences.

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Abstract

For many neurodegenerative disorders, accurate prognosis is challenged by the lack of understanding of intrinsic disease progression. Despite decades of research, the exact mechanisms behind the aggregation processes of protein misfolding are still unknown. Examining each step of this process is vital in determining the anomalies responsible for causing disease and thus developing appropriate treatments. This thesis focuses on the aggregation mechanism of the huntingtin (Htt) protein mutated in Huntington’s disease (HD). The report is divided into three sections, each focusing on an important element in contemporary HD research. The first section encompasses current knowledge on amyloid aggregation and growth processes. The focal point is the toxicity of intermediate and mature protein structures in accordance with environmental and innate factors that influence them. Section two focuses on the contemporary methods and technologies used for research on amyloidosis, with an emphasis on the ThT fluorescence assay and the analysis platform AmyloFit. The biophysical mechanisms of fluorescence analysis are elucidated and the technological limitations are assessed. The third section applies the current knowledge of amyloid behavior of section one with the most up-to-date technologies discussed in section two to an experimental study. The investigation was performed by Dr. Irina Matlahov and recorded Htt amyloid aggregation in diverse salt conditions. Analysis was conducted via thioflavin T fluorescence assay and the online fitting platform AmyloFit. The discussion evaluates the interpreted data in its ability to improve understanding of amyloid aggregation behavior in different environments with the goal of providing further insight into the cellular mechanisms of Htt. The overall focus of this paper is the use of techniques such as the thioflavin T assay and AmyloFit role in improving understanding of molecular interactions and their impact on huntingtin aggregation processes.

Type:	Thesis (--Choose an option--)
Major:	Sciences
Supervisor:	Wel, van der, P.
Datum van aanlevering:	01 Jul 2020 09:22
Last modified:	01 Jul 2020 09:22
URI:	http://ucg.studenttheses.ub.rug.nl/id/eprint/47

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