---
res:
  bibo_abstract:
  - Amyloid formation is linked to devastating neurodegenerative diseases, motivating
    detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated
    with Alzheimer’s disease, the mechanism and rate of aggregation have been established
    for a range of variants and conditions <jats:italic>in vitro</jats:italic> and
    in bodily fluids. A key outstanding question is how the relative stabilities of
    monomers, fibrils and intermediates affect each step in the fibril formation process.
    By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or
    guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying
    microscopic steps and establish the importance of changes in relative stability
    induced by the presence of denaturant for each individual step. Denaturants shift
    the equilibrium towards the unfolded state of each species. We find that a non-ionic
    denaturant, urea, reduces the overall aggregation rate, and that the effect on
    nucleation is stronger than the effect on elongation. Urea reduces the rate of
    secondary nucleation by decreasing the coverage of fibril surfaces and the rate
    of nucleus formation. It also reduces the rate of primary nucleation, increasing
    its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at
    low denaturant concentrations and decelerates the aggregation at high denaturant
    concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic
    interactions between peptides by the charged denaturant dominates, leading to
    an increased aggregation rate. At higher GuHCl concentrations, the electrostatic
    repulsion is completely screened, and the denaturing effect dominates. The results
    illustrate how the differential effects of denaturants on stability of monomer,
    oligomer and fibril translate to differential effects on microscopic steps, with
    the rate of nucleation being most strongly reduced.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Tanja
      foaf_name: Weiffert, Tanja
      foaf_surname: Weiffert
  - foaf_Person:
      foaf_givenName: Georg
      foaf_name: Meisl, Georg
      foaf_surname: Meisl
  - foaf_Person:
      foaf_givenName: Samo
      foaf_name: Curk, Samo
      foaf_surname: Curk
  - foaf_Person:
      foaf_givenName: Risto
      foaf_name: Cukalevski, Risto
      foaf_surname: Cukalevski
  - foaf_Person:
      foaf_givenName: Anđela
      foaf_name: Šarić, Anđela
      foaf_surname: Šarić
      foaf_workInfoHomepage: http://www.librecat.org/personId=bf63d406-f056-11eb-b41d-f263a6566d8b
    orcid: 0000-0002-7854-2139
  - foaf_Person:
      foaf_givenName: Tuomas P. J.
      foaf_name: Knowles, Tuomas P. J.
      foaf_surname: Knowles
  - foaf_Person:
      foaf_givenName: Sara
      foaf_name: Linse, Sara
      foaf_surname: Linse
  bibo_doi: 10.3389/fnins.2022.943355
  bibo_volume: 16
  dct_date: 2022^xs_gYear
  dct_identifier:
  - UT:000866287100001
  dct_isPartOf:
  - http://id.crossref.org/issn/1662-453X
  dct_language: eng
  dct_publisher: Frontiers Media@
  dct_subject:
  - General Neuroscience
  dct_title: Influence of denaturants on amyloid β42 aggregation kinetics@
...