Nakazawa Yasumoto, Suzuki Yu, Williamson Mike P, Saitô Hazime, Asakura Tetsuo
Nature and Science Museum, Tokyo University of Agriculture and Technology, 2-24-16, Nakacho, Koganei, Tokyo, 184-8588 Japan.
Chem Phys Lipids. 2009 Mar;158(1):54-60. doi: 10.1016/j.chemphyslip.2008.12.001. Epub 2008 Dec 24.
Amyloid beta-peptide (Abeta) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate from regions of neuronal membrane rich in gangliosides. We analyzed the mode of interaction of Abeta with lipid bilayers by multinuclear NMR using (31)P nuclei. We found that Abeta (1-40) strongly perturbed the bilayer structure of dimyristoylphosphatidylcholine (DMPC), to form a non-lamellar phase (most likely micellar). The ganglioside GM1 potentiated the effect of Abeta (1-40), as viewed from (31)P NMR. The difference of the isotropic peak intensity between DMPC/Abeta and DMPC/GM1/Abeta suggests a specific interaction between Abeta and GM1. We show that in the DMPC/GM1/Abeta system there are three lipid phases, namely a lamellar phase, a hexagonal phase and non-oriented lipids. The latter two phases are induced by the presence of the Abeta peptide, and facilitated by GM1.
淀粉样β肽（Aβ）是阿尔茨海默病斑块的主要成分，并且有人提出老年斑的形成起源于富含神经节苷脂的神经元膜区域。我们使用³¹P核通过多核核磁共振分析了Aβ与脂质双层的相互作用模式。我们发现Aβ（1 - 40）强烈扰乱了二肉豆蔻酰磷脂酰胆碱（DMPC）的双层结构，形成了非层状相（最可能是胶束相）。从³¹P核磁共振来看，神经节苷脂GM1增强了Aβ（1 - 40）的作用。DMPC/Aβ和DMPC/GM1/Aβ之间各向同性峰强度的差异表明Aβ与GM1之间存在特异性相互作用。我们表明，在DMPC/GM1/Aβ系统中有三种脂质相，即层状相、六方相和无定向脂质。后两种相是由Aβ肽的存在诱导产生的，并由GM1促进形成。
