Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function
Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function
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DOI：
10.1021/acschemneuro.8b00733
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发表时间：
2019-05-01
影响因子：
5
通讯作者：
Bhunia, Anirban
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Dipita;Mohite, Ganesh M.;Bhunia, Anirban
在中枢神经系统(CNS)出现帕金森氏症之前，肠道通透性改变已经与帕金森氏症在肠道神经系统的病理生理相关。肠道细菌释放的炎性内毒素或脂多糖(LPS)通过形成中间成核物质来调节α-突触核蛋白淀粉样蛋白的形成。在这里，生物物理技术结合显微图像揭示了内毒素和无核蛋白之间的分子相互作用，这种相互作用可以诱导快速成核事件。这种异分子相互作用稳定了α-突触核蛋白聚集途径中的α-螺旋中间体。多维核磁共振研究探索了内毒素结合结构基序中的残基，该结构基序调节成核形式，影响细胞内化和相关的细胞毒性。总体而言，我们的数据描述了这种与帕金森病进展中的另一种途径相关的异分子相互作用。
Altered intestinal permeability has been correlated with Parkinson's pathophysiology in the enteric nervous system, before manifestations in the central nervous system (CNS). The inflammatory endotoxin or lipopolysaccharide (LPS) released by gut bacteria is known to modulate alpha-synuclein amyloidogenesis through the formation of intermediate nucleating species. Here, biophysical techniques in conjunction with microscopic images revealed the molecular interaction between lipopolysaccharide and asynuclein that induce rapid nucleation events. This heteromolecular interaction stabilizes the alpha-helical intermediates in the alpha-synuclein aggregation pathway. Multitude NMR studies probed the residues involved in the LPS-binding structural motif that modulates the nucleating forms, affecting the cellular internalization and associated cytotoxicity. Collectively, our data characterizes this heteromolecular interaction associated with an alternative pathway in Parkinson's disease progression.