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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Ono, Kenjiro¹  Takahashi, Ryoichi¹  Ikeda, Tokuhei^1,2  Mizuguchi, Mineyuki³  Hamaguchi, Tsuyoshi¹  Yamada, Masahito¹ 

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol & Aging, Kanazawa, Ishikawa 9208640, Japan

[2] Iou Hosp, Natl Hosp Org, Dept Neurol, Kanazawa, Ishikawa 9200192, Japan

[3] Toyama Univ, Fac Pharmaceut Sci, Sugitani, Toyama 9300194, Japan

关键词: Amyloid beta-protein;    Alzheimer's disease;    Seeding effect;   

DOI  :  10.1016/j.bbadis.2014.01.002

来源: Elsevier

【 摘 要 】

Amyloid beta-protein (A beta) aggregation is considered to be a critical step in the neurodegeneration of Alzheimer's disease (AD). In addition to A beta, many proteins aggregate into the amyloid state, in which they form elongated fibers with spines comprising stranded beta-sheets. However, the cross-seeding effects of other protein aggregates on A beta aggregation pathways are not completely clear. To investigate the cross-seeding effects of exogenous and human non-CNS amyloidogenic proteins on A beta aggregation pathways, we examined whether and how sonicated fibrils of casein, fibroin, sericin, actin, and islet amyloid polypeptide affected A beta 40 and A beta 42 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 A beta with the amyloidogenic proteins. Our results indicate that the amyloidogenic proteins, including those contained in foods and cosmetics, contribute to A beta aggregation by binding to A beta, suggesting their possible roles in the propagation of A beta amyloidosis. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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