α-Synuclein-derived lipoparticles in the study of α-Synuclein amyloid fibril formation
α-Synuclein-derived lipoparticles in the study of α-Synuclein amyloid fibril formation
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DOI：
10.1016/j.chemphyslip.2019.02.009
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Etzkorn, Manuel
中科院分区：
文献类型：
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作者：
Falke, Marcel;Victor, Julian;Etzkorn, Manuel
蛋白质 α-突触核蛋白 (α Syn) 的聚集因其参与帕金森病的病理学而受到极大关注。然而，在体外条件下，α Syn 非常可溶，并且在较长时间内动力学稳定。因此，大多数 α Syn 聚集测定依赖于人为诱导或增强聚集的条件，通常是通过引入非天然条件。已经表明，α Syn 与膜相互作用，并且已经确定了膜可以促进和抑制 α Syn 聚集的条件。研究还表明，α Syn 具有组装脂质-蛋白质颗粒的内在能力，其方式与载脂蛋白形成脂质双层纳米盘的方式类似。在这里，我们表明，这些 α Syn-脂质颗粒（α Syn-LiPs）还可以有效诱导、加速或抑制 α Syn 聚集，具体取决于应用条件。因此，α Syn-LiP 提供了一个通用平台和附加工具，与其他设置互补，用于研究 α Syn 淀粉样蛋白原纤维形成的各个方面。
Aggregation of the protein alpha-Synuclein (alpha Syn) is of great interest due to its involvement in the pathology of Parkinson's disease. However, under in vitro conditions alpha Syn is very soluble and kinetically stable for extended time periods. As a result, most alpha Syn aggregation assays rely on conditions that artificially induce or enhance aggregation, often by introducing rather non-native conditions. It has been shown that alpha Syn interacts with membranes and conditions have been identified in which membranes can promote as well as inhibit alpha Syn aggregation. It has also been shown that alpha Syn has the intrinsic capability to assemble lipid-protein-particles, in a similar way as apolipoproteins can form lipid-bilayer nanodiscs. Here we show that these alpha Syn-lipid particles (alpha Syn-LiPs) can also effectively induce, accelerate or inhibit alpha Syn aggregation, depending on the applied conditions. alpha Syn-LiPs therefore provide a general platform and additional tool, complementary to other setups, to study various aspects of alpha Syn amyloid fibril formation.