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

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• 作者：Kenjiro Ono^a ; Ryoichi Takahashi^a ; Tokuhei Ikeda^a ; ^b ; Mineyuki Mizuguchi^c ; Tsuyoshi Hamaguchi^a ; Masahito Yamada^a ; ^{m-yamada@med.kanazawa-u.ac.jp" class="auth_mail}
• 关键词：A尾 ; amyloid 尾-protein ; AD ; Alzheimer's disease ; Act ; actin ; 伪S ; 伪-synuclein ; Cas ; casein ; EM ; electron microscopy ; Fibro ; fibroin ; fA尾 ; A尾 fibrils ; fAct ; Act fibrils ; fCas ; casein fibrils ; fFibro ; fibroin fibrils ; fIAPP ; IAPP fibrils ; fSer ; sericin fibrils ; HSQC ; heteronuclear single quantum coherence ; IAPP ; islet amyloid polypeptide ; NMR ; nuclear magnetic resonance ; Ser ; sericin ; ThT ; thioflavin T
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：April, 2014
• 年：2014
• 卷：1842
• 期：4
• 页码：646-653
• 全文大小：1448 K

文摘

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