Smoking and Parkinson's disease: Does nicotine affect α-synuclein fibrillation?
Smoking and Parkinson's disease: Does nicotine affect α-synuclein fibrillation?
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DOI：
10.1016/j.bbapap.2008.09.026
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发表时间：
2009-02-01
影响因子：
3.2
通讯作者：
Uversky, Vladimir N.
中科院分区：
文献类型：
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作者：
Hong, Dong-Pyo;Fink, Anthony L.;Uversky, Vladimir N.
α-突触核蛋白是一种小的突触前蛋白（14，460 D），其大量分布在大脑中。虽然其功能尚不清楚，但α-突触核蛋白的聚集形式是包括帕金森病（PD）在内的几种神经退行性疾病的病理标志。流行病学研究表明，吸烟可以降低帕金森病的发病率，这表明烟雾可能含有保护神经的化学物质。研究了与香烟烟雾中发现的五种不同化合物有关的α-突触核蛋白的原纤化：假木贼碱、可替宁、对苯二酚、尼古丁和去甲尼古丁。硫磺素T测定，凝胶电泳，尺寸排阻色谱-高效液相色谱法（SEC-HPLC）和原子力显微镜（AFM）被用来监测α-突触核蛋白纤维化的速率和香烟烟雾成分的抑制作用。我们发现，尼古丁和氢醌抑制α-突触核蛋白原纤维形成的浓度依赖性的方式，尼古丁更有效。SEC-HPLC数据显示尼古丁和氢醌稳定可溶性低聚物。通过AFM评价由尼古丁稳定的低聚物的形态，其显示存在三种稳定的低聚物，平均高度为16 nm、10 nm和4 nm。对于香烟烟雾组分对A53 T突变体原纤化的影响，获得了可比较的结果。这些结果表明，尼古丁和氢醌抑制α-突触核蛋白原纤化并稳定可溶性低聚物形式。这些信息可用于了解尼古丁和氢醌作用的分子机制，以开发PD的治疗方案。(C)2008 Elsevier B. V.保留所有权利。
alpha-synuclein is a small presynaptic protein (14,460 D) that is abundantly distributed in the brain. Although, its function is unknown, the aggregated form of alpha-synuclein is a pathological hallmark of several neurodegenerative diseases, including Parkinson's disease (PD). Epidemiological studies have shown that smoking can lessen the incidence of Parkinson's disease, indicating that smoke may contain chemicals that are neuro-protective. The fibrillation of alpha-synuclein was studied in relation to five different compounds found in cigarette smoke: anabasine, cotinine, hydroquinone, nicotine and nornicotine. Thioflavin T assays, gel electrophoresis, size exclusion chromatography-high performance liquid chromatography (SEC-HPLC) and atomic force microscopy (AFM) were utilized to monitor the rate of alpha-synuclein fibrillation and the inhibitory effects of the cigarette smoke components. We show that nicotine and hydroquinone inhibit alpha-synuclein fibril formation in a concentration-dependent manner, with nicotine being more effective. The SEC-HPLC data show that nicotine and hydroquinone stabilize soluble oligomers. The morphology of the oligomers stabilized by nicotine was evaluated by AFM, which showed the presence of three stable oligomers with an average height of 16 nm, 10 nm and 4 nm. comparable results were obtained for the effect of the cigarette smoke components on the A53T mutant fibrillation. These results show that nicotine and hydroquinone inhibit alpha-synuclein fibrillation and stabilize soluble oligomeric forms. This information can be used to understand the molecular mechanism of the nicotine and hydroquinone action to develop therapeutic solutions for PD. (C) 2008 Elsevier B.V. All rights reserved.