Details

Autor(en) / Beteiligte

• Taş, Karin
• Volta, Beatrice Dalla
• Lindner, Christina
• El Bounkari, Omar
• Hille, Kathleen
• Tian, Yuan
• Puig-Bosch, Xènia
• Ballmann, Markus
• Hornung, Simon
• Ortner, Martin
• Prem, Sophia
• Meier, Laura
• Rammes, Gerhard
• Haslbeck, Martin
• Weber, Christian
• Megens, Remco T. A.
• Bernhagen, Jürgen
• Kapurniotu, Aphrodite

Titel

Designed peptides as nanomolar cross-amyloid inhibitors acting via supramolecular nanofiber co-assembly

Ist Teil von

• Nature communications, 2022-08, Vol.13 (1), p.5004-5004, Article 5004

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract 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.