Aggregation of amyloid-[Formula: see text] (Aβ) peptides, cleaved from the amyloid precursor protein, is known as a precursor of the Alzheimer's disease (AD). It is also known that Alzheimer's disease is characterized by a substantial decrease of the amount of polyunsaturated lipids in the neuronal membranes of the frontal gray matter. To get insight into possible interconnection of these phenomena, we have carried out molecular dynamics simulations of two fragments of A[Formula: see text] peptide, A[Formula: see text][Formula: see text] and A[Formula: see text][Formula: see text], in four different lipid bilayers: two monocomponent ones (14:0-14:0 PC, 18:0-22:6 PC), and two bilayers containing mixtures of 18:0-18:0 PE, 22:6-22:6 PE, 16:0-16:0 PC and 18:1-18:1 PC lipids of composition mimicking neuronal membranes in a "healthy" and "AD" brain. The simulations showed that the presence of lipids with highly unsaturated 22:6cis fatty acids chains strongly affects the interaction of amyloid-[Formula: see text] peptides with lipid membranes. The polyunsaturated lipids cause stronger adsorption of A[Formula: see text]-peptides by the membrane and lead to weaker binding between peptides when the latter form aggregates. This difference in the behaviour observed in monocomponent bilayers is propagated in a similar fashion to the mixed membranes mimicking composition of neuronal membranes in "healthy" and "AD" brains, with "healthy" membrane having higher fraction of polyunsaturated lipids. Our simulations give strong indication that it can be physical-chemical background of the interconnection between amyloid fibrillization causing Alzheimer's disease, and content of polyunsaturated lipids in the neuronal membranes.

中文翻译：

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脂质饱和度对神经元膜中淀粉样蛋白-β肽分配和聚集的影响：分子动力学模拟。

淀粉样蛋白的聚集-[公式：见正文] (Aβ) 肽，从淀粉样蛋白前体蛋白中切割下来，被称为阿尔茨海默病 (AD) 的前体。还已知阿尔茨海默病的特征在于额叶灰质的神经元膜中多不饱和脂质的量显着减少。为了深入了解这些现象的可能相互联系，我们对 A[公式：见文本] 肽段的两个片段、A[公式：见文本][公式：见文本]和 A[公式：见文本]进行了分子动力学模拟][公式：见正文]，在四种不同的脂质双层中：两种单组分（14:0-14:0 PC，18:0-22:6 PC）和两个含有 18:0-18:0 混合物的双层PE、22:6-22:6 PE、16:0-16:0 PC 和 18:1-18:1 PC 组成模拟“健康”中的神经元膜的脂质 和“AD”大脑。模拟表明，具有高度不饱和 22:6 顺式脂肪酸链的脂质的存在强烈影响淀粉样蛋白-[公式：见正文]肽与脂质膜的相互作用。多不饱和脂质导致 A[公式：见正文]-肽被膜更强的吸附，并导致当后者形成聚集体时肽之间的结合较弱。在单组分双层中观察到的这种行为差异以类似于“健康”和“AD”大脑中模拟神经元膜组成的混合膜的方式传播，其中“健康”膜具有更高比例的多不饱和脂质。