Exogenous amyloidogenic proteins function as seeds in amyloid β-protein aggregation.
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.
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Kenjiro
K
Ono
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Ryoichi
R
Takahashi
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan; Department of Neurology, National Hospital Organization Iou Hospital, Kanazawa 920-0192, Japan.
Tokuhei
T
Ikeda
Faculty of Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
Mineyuki
M
Mizuguchi
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Tsuyoshi
T
Hamaguchi
Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan. Electronic address: m-yamada@med.kanazawa-u.ac.jp.
Masahito
M
Yamada
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D058227:Amyloidogenic Proteins / Q000494:pharmacology*; D000686:Amyloidosis / Q000209:etiology; D052160:Benzothiazoles; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T
Alzheimer's disease; Amyloid β-protein; Seeding effect