TY - JOUR
T1 - Exogenous amyloidogenic proteins function as seeds in amyloid β-protein aggregation
AU - Ono, Kenjiro
AU - Takahashi, Ryoichi
AU - Ikeda, Tokuhei
AU - Mizuguchi, Mineyuki
AU - Hamaguchi, Tsuyoshi
AU - Yamada, Masahito
N1 - Funding Information:
This work has been supported by Grants-in-Aid for Challenging Exploratory Research ( 22659170 ) (M.Y.), Scientific Research (B) ( 20390242 ) (M.Y.), Young Scientists (B) (K.O.), and Knowledge Cluster Initiative [High-Tech Sensing and Knowledge Handling Technology (Brain Technology)] (M.Y.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, Japan , a grant to the Amyloidosis Research Committee from the Ministry of Health, Labour, and Welfare, Japan (M.M., M.Y.), Novartis Foundation for Gerontological Research (K.O.), Takeda Science Foundation (K.O.), and Nagao Memorial fund (K.O.).
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid β-protein
KW - Seeding effect
UR - http://www.scopus.com/inward/record.url?scp=84893485687&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2014.01.002
DO - 10.1016/j.bbadis.2014.01.002
M3 - 学術論文
C2 - 24440525
AN - SCOPUS:84893485687
SN - 0925-4439
VL - 1842
SP - 646
EP - 653
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 4
ER -