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Secondary Nucleation in Amyloid Formation

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Author

Summary, in English

Research into Alzheimer's disease is still hampered by a lack of fundamental understanding of the underlying mechanisms. While the aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is highly implicated as a key factor in the disease, the molecular nature of its involvement has proven complex and elusive. This thesis and the work herein is part of an ongoing effort to map out the aggregation mechanism of Aβ in vitro in as much detail as possible, in the hope to provide a better basis for understanding its role in disease. In particular, the mechanism of secondary nucleation, whereby the fibril surface catalyses the formation of new fibrils is of interest due to its capacity to generate large numbers of toxic oligomers. In this work, we probe the determinants of secondary nucleation by studying its influence in different temperatures and pH and we confirm that it remains an important factor in aggregation in human cerebrospinal fluid. We also report a transient accumulation of pre-fibrillar aggregates, likely to be a result of heavily saturated secondary nucleation, which can form a basis for further structural studies of this phenomenon.

Publishing year

2020-05-11

Language

English

Document type

Dissertation

Publisher

Lund University, Faculty of Science, Department of Chemistry

Topic

  • Other Chemistry Topics

Keywords

  • Alzheimer's disease
  • amyloid
  • Ab42
  • aggregation mechanism
  • aggregation kinetics
  • secondary nucleation
  • Protein misfolding

Status

Published

ISBN/ISSN/Other

  • ISBN: 978-91-7422-747-5
  • ISBN: 978-91-7422-740-6

Defence date

4 June 2020

Defence time

15:00

Defence place

Lecture Hall A, Kemicentrum, Naturvetarvägen 14, Lund (Live streaming: https://lu-se.zoom.us/j/64932035028)

Opponent

  • David Eisenberg (Professor)