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首页> 外文期刊>Biochemistry >Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid membranes.
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Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid membranes.

机译:加速淀粉样蛋白β蛋白在氧化损伤脂质膜上的积累。

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摘要

The fully developed lesion of Alzheimer's Disease is a dense plaque composed of fibrillar amyloid beta-proteins with a characteristic and well-ordered beta-sheet secondary structure. Because the incipient lesion most likely develops when these proteins are first induced to form beta-sheet secondary structure, it is important to understand factors that induce amyloid beta-proteins to adopt this conformation. In this investigation we used a novel form of infrared spectroscopy that can characterize the conformation, orientation, and rate of accumulation of the protein on various lipid membranes to determine whether oxidatively damaged phospholipid membranes induce the formation of beta-sheet secondary structure in a 42-residue amyloid beta-protein. We found that membranes containing oxidatively damaged phospholipids accumulated amyloid beta-protein significantly faster than membranes containing only unoxidized or saturated phospholipids. Accelerated accumulation was also seen when 3 mol % G(M1) ganglioside was incorporated into a saturated phosphatidylcholine membrane. The accumulated protein more completely adopted a beta-sheet conformation on oxidized membranes, and the plane of the beta-sheet was oriented parallel to the plane of the membrane. These results indicate that oxidatively damaged phospholipid membranes promote beta-sheet formation by amyloid beta-proteins, and they suggest a possible role for lipid peroxidation in the pathogenesis of Alzheimer's Disease.
机译:Alzheimer疾病的完全发育的病变是由具有特征和良好有序的β-薄膜二级结构组成的抗纤维淀粉样蛋白β-蛋白质的致密斑块。因为首先诱导这些蛋白质以形成β-片二次结构时,初期的病变最有可能发生,所以要了解诱导淀粉样蛋白β-蛋白采用这种构象的因素是重要的。在该研究中,我们使用了一种新颖的红外光谱,可以表征各种脂质膜对蛋白质的构象,取向和积累速率,以确定氧化损坏的磷脂膜是否诱导42-中β二次结构的形成。残留淀粉样蛋白β-蛋白。我们发现含有氧化受损的磷脂的膜累积淀粉样蛋白β-蛋白,显着比含有不氧化或饱和磷脂的膜更快。当3摩尔%G(M1)神经节苷脂掺入饱和磷脂酰胆碱膜中时,还可以看到加速积累。累积的蛋白质更完全采用氧化膜的β-片状构象,并且β-片的平面平行于膜的平面定向。这些结果表明,氧化受损的磷脂膜促进淀粉样蛋白β-蛋白的β-片状形成,并且它们表明脂质过氧化在阿尔茨海默病的发病机制中可能作用。

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