Kasai Shingo, Urushibata Shunsuke, Hozumi Kentaro, Yokoyama Fumiharu, Ichikawa Naoki, Kadoya Yuichi, Nishi Norio, Watanabe Nobuhisa, Yamada Yoshihiko, Nomizu Motoyoshi
Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.
Biochemistry. 2007 Apr 3;46(13):3966-74. doi: 10.1021/bi062097t. Epub 2007 Mar 10.
Amyloid fibril formation is associated with several pathologies, including Alzheimer's disease, Parkinson's disease, type II diabetes, and prion diseases. Recently, a relationship between basement membrane components and amyloid deposits has been reported. The basement membrane protein, laminin, may be involved in amyloid-related diseases, since laminin is present in amyloid plaques in Alzheimer's disease and binds to amyloid precursor protein. Recently, we showed that peptide A208 (AASIKVAVSADR), the IKVAV-containing peptide, formed amyloid-like fibrils. We previously identified 60 cell adhesive sequences in laminin-1 using a total of 673 12-mer synthetic peptides. Here, we screened for additional amyloidogenic sequences among 60 cell adhesive peptides derived from laminin-1. We first examined amyloid-like fibril formation by the 60 active peptides with Congo red, a histological dye binding to many amyloid-like proteins. Thirteen peptides were stained with Congo red. Four of the 13 peptides promoted cell attachment and neurite outgrowth like the IKVAV-containing peptide. The four peptides also showed amyloid-like fibril formation in both X-ray diffraction and electron microscopic analyses. The amyloidogenic peptides contain consensus amino acid components, including both basic and acidic amino acids and Ser and Ile residues. These results indicate that at least five laminin-derived peptides can form amyloid-like fibrils. We conclude that the laminin-derived amyloidogenic peptides have the potential to form amyloid-like fibrils in vivo, possibly when laminin-1 is degraded.
淀粉样纤维的形成与多种病理学状况相关，包括阿尔茨海默病、帕金森病、II型糖尿病和朊病毒病。最近，有报道称基底膜成分与淀粉样沉积物之间存在关联。基底膜蛋白层粘连蛋白可能参与淀粉样相关疾病，因为层粘连蛋白存在于阿尔茨海默病的淀粉样斑块中，并与淀粉样前体蛋白结合。最近，我们发现含IKVAV的肽A208（AASIKVAVSADR）形成了淀粉样纤维。我们之前使用总共673个12肽合成肽在层粘连蛋白-1中鉴定出60个细胞黏附序列。在此，我们在源自层粘连蛋白-1的60个细胞黏附肽中筛选额外的淀粉样生成序列。我们首先用刚果红检测60个活性肽是否形成淀粉样纤维，刚果红是一种能与许多淀粉样蛋白结合的组织学染料。13个肽被刚果红染色。这13个肽中的4个像含IKVAV的肽一样促进细胞黏附和神经突生长。这4个肽在X射线衍射和电子显微镜分析中也显示出淀粉样纤维的形成。这些淀粉样生成肽含有共有氨基酸成分，包括碱性和酸性氨基酸以及丝氨酸和异亮氨酸残基。这些结果表明至少5个源自层粘连蛋白的肽能形成淀粉样纤维。我们得出结论，源自层粘连蛋白的淀粉样生成肽在体内有形成淀粉样纤维的潜力，可能在层粘连蛋白-1降解时发生。
