Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.
Biophys Chem. 2013 Dec 1;182:23-9. doi: 10.1016/j.bpc.2013.07.010. Epub 2013 Aug 14.
Beta-amyloid (1-40) is one of the two most abundant species of amyloid-beta peptides present as fibrils in the extracellular senile plaques in the brain of Alzheimer's patients. Recently, the molecular aggregates constituting the early stage of fibril formation, i.e., oligomers and protofibrils, have been investigated as the main responsible for amyloid-beta cytotoxic effect. The molecular mechanism leading to neurodegeneration is still under debate, and it is common opinion that it may reside in the interaction between amyloid species and the neural membrane. In this investigation Atomic Force Microscopy and spectroscopy have been used to understand how structural (and mechanical) properties of POPC/POPS lipid bilayers, simulating the phospholipid composition and negative net charge of neuritic cell membranes, are influenced by the interaction with Aβ(1-40), in different stages of the peptide aggregation. Substantial differences in the damage caused to the lipid bilayers have been observed, confirming the toxic effect exerted especially by Aβ(1-40) prefibrillar oligomers.
β-淀粉样蛋白（1-40）是两种最丰富的淀粉样β肽之一，以纤维的形式存在于阿尔茨海默病患者大脑中的细胞外老年斑中。最近，构成纤维形成早期阶段的分子聚集体，即低聚物和原纤维，已被研究为淀粉样β细胞毒性作用的主要原因。导致神经退行性变的分子机制仍存在争议，人们普遍认为它可能存在于淀粉样蛋白与神经膜的相互作用中。在这项研究中，原子力显微镜和光谱学被用于了解 POPC/POPS 脂质双层的结构（和机械）特性，模拟神经突细胞膜的磷脂组成和负净电荷，如何受到与 Aβ（1-40）相互作用的影响，在肽聚集的不同阶段。已经观察到脂质双层所造成的损伤有很大的差异，这证实了 Aβ（1-40）前纤维状低聚物所发挥的特别毒性作用。
