Designed peptides as nanomolar cross-amyloid inhibitors acting via supramolecular nanofiber co-assembly.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 08 2022
25 08 2022
Historique:
received:
16
01
2022
accepted:
10
08
2022
entrez:
25
8
2022
pubmed:
26
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
Amyloid self-assembly is linked to numerous devastating cell-degenerative diseases. However, designing inhibitors of this pathogenic process remains a major challenge. Cross-interactions between amyloid-β peptide (Aβ) and islet amyloid polypeptide (IAPP), key polypeptides of Alzheimer's disease (AD) and type 2 diabetes (T2D), have been suggested to link AD with T2D pathogenesis. Here, we show that constrained peptides designed to mimic the Aβ amyloid core (ACMs) are nanomolar cross-amyloid inhibitors of both IAPP and Aβ42 and effectively suppress reciprocal cross-seeding. Remarkably, ACMs act by co-assembling with IAPP or Aβ42 into amyloid fibril-resembling but non-toxic nanofibers and their highly ordered superstructures. Co-assembled nanofibers exhibit various potentially beneficial features including thermolability, proteolytic degradability, and effective cellular clearance which are reminiscent of labile/reversible functional amyloids. ACMs are thus promising leads for potent anti-amyloid drugs in both T2D and AD while the supramolecular nanofiber co-assemblies should inform the design of novel functional (hetero-)amyloid-based nanomaterials for biomedical/biotechnological applications.
Identifiants
pubmed: 36008417
doi: 10.1038/s41467-022-32688-0
pii: 10.1038/s41467-022-32688-0
pmc: PMC9411207
doi:
Substances chimiques
Amyloid
0
Amyloid beta-Peptides
0
Amyloidogenic Proteins
0
Islet Amyloid Polypeptide
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5004Informations de copyright
© 2022. The Author(s).
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