Exogenous amyloidogenic proteins function as seeds in amyloid β-protein aggregation

Kenjiro Ono, Ryoichi Takahashi, Tokuhei Ikeda, Mineyuki Mizuguchi, Tsuyoshi Hamaguchi, Masahito Yamada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Amyloid β-protein (Aβ) aggregation is considered to be a critical step in the neurodegeneration of Alzheimer's disease (AD). In addition to Aβ, many proteins aggregate into the amyloid state, in which they form elongated fibers with spines comprising stranded β-sheets. However, the cross-seeding effects of other protein aggregates on Aβ aggregation pathways are not completely clear. To investigate the cross-seeding effects of exogenous and human non-CNS amyloidogenic proteins on Aβ aggregation pathways, we examined whether and how sonicated fibrils of casein, fibroin, sericin, actin, and islet amyloid polypeptide affected Aβ40 and Aβ42 aggregation pathways using the thioflavin T assay and electron microscopy. Interestingly, the fibrillar seeds of all amyloidogenic proteins functioned as seeds. The cross-seeding effect of actin was stronger but that of fibroin was weaker than that of other proteins. Furthermore, our nuclear magnetic resonance spectroscopic studies identified the binding sites of Aβ with the amyloidogenic proteins. Our results indicate that the amyloidogenic proteins, including those contained in foods and cosmetics, contribute to Aβ aggregation by binding to Aβ, suggesting their possible roles in the propagation of Aβ amyloidosis.

Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1842
Issue number4
DOIs
StatePublished - 2014/04

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Seeding effect

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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