Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742045
Title: A multi-disciplinary study of the early stages of beta amyloid aggregation
Author: Mancini, Onorio Claudio
ISNI:       0000 0004 7226 1154
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Amyloid fibrils have been linked to many diseases, with different proteins being associated with different health issues. The aggregation of Beta Amyloid (Aß) peptides can lead to Alzheimer’s disease. These peptides are found in the body naturally, although Aß function is still not clear. The aggregation process is still a matter of research, however it is widely accepted that a lag period is followed by rapid aggregate growth and then a saturation phase where growth halts. Understanding how and why this happens is imperative for disease prevention. It has been found that toxicity occurs during the formation of oligomer. Collaborative work involving simulation and experimental methods has become commonplace, improving the understanding of this process. Consequently, the work presented here is a multidisciplinary study of the early stages of amyloid aggregation in Aß1-40 and Aß1-42. These are the two most common species and are 40 and 42 amino acid groups long respectively. They have been studied through the use of Molecular Dynamics (MD) and Monte Carlo (MC) simulations, which have been complemented by probing Aß1-40 with the experimental methods: fluorescence spectroscopy, fluorescence anisotropy and dynamic light scattering. Experimentation proved challenging, due to the noise encountered in Aß samples and alternative solvent compositions were studied in an attempt to overcome this. These experiments had limited success but when combined with simulation models, revealed potential insight into the aggregation through the movements of the tyrosine (Tyr) side-chain, an amino acid group found in the Aß proteins. MD simulations and MC simulations were used in order to probe the underlying mechanisms surrounding Tyr movements and their environments during the aggregation process and how it affects fluorescence anisotropy. The MD simulations also revealed conformational changes in the protein due to the presence of ions and discovered two new Tyr orientations which occur in protofibrils.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.742045  DOI:
Share: