The effect of Alzheimer's Aβ aggregation state on the permeation of biomimetic lipid vesicles.
The effect of Alzheimer's Aβ aggregation state on the permeation of biomimetic lipid vesicles.
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阿尔茨海默病 Aβ 聚集状态对仿生脂质囊泡渗透的影响。
DOI：
10.1021/la101581g
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
L. Serpell
中科院分区：
文献类型：
--
作者：
Thomas L. Williams;I. J. Day;L. Serpell
阿尔茨海默病的特征在于Aβ肽的聚集和沉积。这种40或42个残基的肽是淀粉样前体蛋白膜蛋白的蛋白水解产物，并且能够组装形成有序的、稳定的淀粉样原纤维以及小的、可溶的和潜在的细胞毒性寡聚体。低聚物的毒性可能与结合至脂质膜并影响脂质膜的完整性的能力有关。在这项新的工作中，我们使用填充染料的合成囊泡监测和比较了强效Aβ42肽、淀粉样蛋白生成较少的Aβ40肽和淀粉样蛋白生成减少的变体与膜结合并影响膜完整性的能力。我们揭示了组装的效力随着肽的孵育时间而降低，并且当通过电子显微镜观察到特定物种时发生最大效应。我们已经研究了脂质囊泡组合物的影响，我们的结果表明，囊泡上的电荷是重要的，结合可能部分介导的GM1神经节苷脂受体在脊椎动物膜的外叶中表达。
Alzheimer's disease is characterized by the aggregation and deposition of the Aβ peptide. This 40 or 42 residue peptide is the product of the proteolysis of the amyloid precursor protein membrane protein and is able to assemble to form ordered, stable amyloid fibrils as well as small, soluble, and potentially cytotoxic oligomers. The toxicity of the oligomers may be associated with the ability to bind to and affect the integrity of lipid membranes. In this novel work, we have monitored and compared the ability of the potent Aβ42 peptide, the less amyloidogenic Aβ40 peptide, and a variant with reduced amyloidogenicity to bind to and affect the integrity of membranes using dye-filled synthetic vesicles. We reveal that the potency of the assemblies reduces with incubation time of the peptide and that maximal effect occurs when a particular species is apparent by electron microscopy. We have investigated the effect of lipid vesicle composition, and our results suggest that charge on the vesicles is important and that binding may partly be mediated by the GM1 ganglioside receptors expressed in the outer leaflet of vertebrate membranes.