Secondary Nucleation in Amyloid Formation

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Abstract

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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Annan kemi

Nyckelord

Originalspråkengelska
KvalifikationDoktor
Handledare/Biträdande handledare
Tilldelningsdatum2020 jun 4
UtgivningsortLund
Förlag
  • Lund University, Faculty of Science, Department of Chemistry
Tryckta ISBN978-91-7422-740-6
Elektroniska ISBN978-91-7422-747-5
StatusPublished - 2020 maj 11
PublikationskategoriForskning

Nedladdningar

Ingen tillgänglig data

Relaterad forskningsoutput

Rebecca Frankel, Mattias Törnquist, Georg Meisl, Oskar Hansson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow, Birgitta Frohm, Tommy Cedervall, Tuomas P.J. Knowles, Thom Leiding & Sara Linse, 2019, I : Communications Biology. 2, 1, 365.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Samuel I.A. Cohen, Risto Cukalevski, Thomas C.T. Michaels, A. Šarić, Mattias Törnquist, Michele Vendruscolo, Christopher M. Dobson, Alexander K. Buell, Tuomas P.J. Knowles & Sara Linse, 2018 maj 1, I : Nature Chemistry. 10, 5, s. 523-531 9 s.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Mattias Törnquist, Thomas C.T. Michaels, Kalyani Sanagavarapu, Xiaoting Yang, Georg Meisl, Samuel I.A. Cohen, Tuomas P.J. Knowles & Sara Linse, 2018, I : Chemical Communications. 54, 63, s. 8667-8684 18 s.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Visa alla (3)