Modulation of Aβ42 Aggregation Kinetics and Pathway by Low-Molecular-Weight Inhibitors.
NMR spectroscopy
aggregation
amyloid beta-peptides
inhibitors
kinetics
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
03 04 2023
03 04 2023
Historique:
revised:
18
01
2023
received:
04
01
2023
medline:
4
4
2023
pubmed:
19
1
2023
entrez:
18
1
2023
Statut:
ppublish
Résumé
The aggregation of amyloid-β 42 (Aβ42) is directly related to the pathogenesis of Alzheimer's disease. Here, we have investigated the early stages of the aggregation process, during which most of the cytotoxic species are formed. Aβ42 aggregation kinetics, characterized by the quantification of Aβ42 monomer consumption, were tracked by real-time solution NMR spectroscopy (RT-NMR) allowing the impact that low-molecular-weight (LMW) inhibitors and modulators exert on the aggregation process to be analysed. Distinct differences in the Aβ42 kinetic profiles were apparent and were further investigated kinetically and structurally by using thioflavin T (ThT) and transmission electron microscopy (TEM), respectively. LMW inhibitors were shown to have a differential impact on early-state aggregation. Insight provided here could direct future therapeutic design based on kinetic profiling of the process of fibril formation.
Identifiants
pubmed: 36652672
doi: 10.1002/cbic.202200760
doi:
Substances chimiques
amyloid beta-protein (1-42)
0
Amyloid beta-Peptides
0
Peptide Fragments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200760Informations de copyright
© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.
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