多巴胺不能促进未氧化α-突触核蛋白的寡聚

S. Shimotakahara, M. Matsui, C. Sakuma, Teruaki Takahashi, T. Fujimoto, K. Furihata, M. Kojima, Shohei Seino, T. Machinami, Y. Shibusawa, K. Uéda, M. Tashiro
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引用次数: 2

摘要

α-突触核蛋白是丝状路易小体和路易神经突的主要成分,它们决定了帕金森病和路易小体痴呆的神经病理特征。为了研究α-突触核蛋白与多巴胺(DA)相关的低聚过程,利用核磁共振和其他生物物理技术研究了α-突触核蛋白形成低聚物的结构倾向。h - 15n HSQC光谱表明,N端和c端均与DA相互作用。虽然ESI-MS也观察到在谷胱甘肽存在的情况下与DA的相互作用,但在尺寸排除色谱中观察到寡聚化的显著抑制,这表明α-突触核蛋白的氧化是其寡聚化的必要条件。
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Dopamine cannot promote oligomerization of unoxidized α-synuclein
α-Synuclein is the major component of the filamentous Lewy bodies and Lewy neurites that define neuropathological features of Parkinson’s disease and dementia with Lewy bodies. To investigate the oligomerization process of α-synuclein in association with dopamine (DA), the structural propensities to form oligomers were studied using NMR and other biophysical techniques. The1H-15N HSQC spectra indicated that both N- and C-termini interacted with DA. Although interactions with DA were also observed in the presence of glutathione by ESI-MS, the significant suppression of oligomerization was observed in the size exclusion chromatography, suggesting that oxidations of α-synuclein are required for its oligomerization.
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