Anti-fibrillogenic and fibril-destabilizing activity of nicotine in vitro: Implications for the prevention and therapeutics of Lewy body diseases
Anti-fibrillogenic and fibril-destabilizing activity of nicotine in vitro: Implications for the prevention and therapeutics of Lewy body diseases
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DOI：
10.1016/j.expneurol.2007.03.002
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Yamada, Masahito
中科院分区：
文献类型：
--
作者：
Ono, Kenjiro;Hirohata, Mie;Yamada, Masahito
α -突触核蛋白（α S）的聚集被认为是路易体疾病（LBD）和多系统萎缩（MSA）发展的关键步骤。回顾性和前瞻性流行病学研究一致表明吸烟与帕金森病（PD）呈负相关。我们利用荧光光谱、电子显微镜和原子力显微镜研究了尼古丁、吡啶和n -甲基吡啶对野生型α S （α S (WT)）和A53T突变型α S （A53T）形成α S原纤维（f α S）的影响，以及对预形成的f α S的影响。尼古丁剂量依赖性地抑制α S （WT）和A53T形成f α S。此外，尼古丁剂量依赖性地破坏了预形成的α - Ss。尼古丁的这些作用与n -甲基吡咯啶的作用相似。尼古丁的抗纤原活性可能不仅通过抑制f - α S的形成，还可能通过破坏已形成的f - α S的不稳定来发挥作用。此外，这种作用可能与尼古丁的n -甲基吡罗啉部分有关。(c) 2007爱思唯尔公司版权所有。
The aggregation of alpha-synuclein (alpha S) has been implicated as a critical step in the development of Lewy body diseases (LBD) and multiple system atrophy (MSA). Both retrospective and prospective epidemiological studies have consistently demonstrated an inverse association between cigarette smoking and Parkinson's disease (PD). We used fluorescence spectroscopy with thioflavin S, electron microscopy and atomic force microscopy to examine the effects of nicotine, pyridine, and N-methylpyrrolidine on the formation of alpha S fibrils (f alpha S) from wild-type alpha S (alpha S (WT)) and A53T mutant alpha S (A53T) and on preformed f alpha Ss. Nicotine dose-dependently inhibited the f alpha S formation from both alpha S (WT) and A53T. Moreover, nicotine dose-dependently destabilized preformed f alpha Ss. These effects of nicotine were similar to those of N-methylpyrroli dine. The anti-fibrillogenic activity of nicotine may be exerted not only by the inhibition of f alpha S formation but also by the destabilization of preformed f alpha S. Additionally, this effect may be attributed to N-methylpyrrolicline moieties of nicotine. (c) 2007 Elsevier Inc. All rights reserved.