Department of Genome Sciences and Chemistry, University of Washington, Seattle, Washington 98195, USA.
J Neurosci. 2010 Apr 21;30(16):5525-32. doi: 10.1523/JNEUROSCI.4777-09.2010.
Epidemiological studies have revealed a significantly reduced risk of Parkinson's disease (PD) among coffee and tobacco users, although it is unclear whether these correlations reflect neuroprotective/symptomatic effects of these agents or preexisting differences in the brains of tobacco and coffee users. Here, we report that coffee and tobacco, but not caffeine or nicotine, are neuroprotective in fly PD models. We further report that decaffeinated coffee and nicotine-free tobacco are as neuroprotective as their caffeine and nicotine-containing counterparts and that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco are also evident in Drosophila models of Alzheimer's disease and polyglutamine disease. Finally, we report that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco require the cytoprotective transcription factor Nrf2 and that a known Nrf2 activator in coffee, cafestol, is also able to confer neuroprotection in our fly models of PD. Our findings indicate that coffee and tobacco contain Nrf2-activating compounds that may account for the reduced risk of PD among coffee and tobacco users. These compounds represent attractive candidates for therapeutic intervention in PD and perhaps other neurodegenerative diseases.
流行病学研究表明，咖啡和烟草使用者患帕金森病 (PD) 的风险显著降低，尽管尚不清楚这些相关性是否反映了这些药物的神经保护/症状缓解作用，还是烟草和咖啡使用者大脑中预先存在的差异。在这里，我们报告咖啡和烟草具有神经保护作用，但咖啡因和尼古丁没有这种作用，在果蝇 PD 模型中亦是如此。我们进一步报告说，脱咖啡因咖啡和无尼古丁烟草与含咖啡因和尼古丁的同类产品具有相同的神经保护作用，脱咖啡因咖啡和无尼古丁烟草的神经保护作用在阿尔茨海默病和多聚谷氨酰胺疾病的果蝇模型中也很明显。最后，我们报告说，脱咖啡因咖啡和无尼古丁烟草的神经保护作用需要细胞保护转录因子 Nrf2，而咖啡中的一种已知的 Nrf2 激活剂——咖啡醇也能够在我们的 PD 果蝇模型中提供神经保护。我们的研究结果表明，咖啡和烟草中含有 Nrf2 激活化合物，这可能解释了咖啡和烟草使用者患 PD 的风险降低。这些化合物代表了治疗 PD 甚至其他神经退行性疾病的有吸引力的候选药物。
