Center for Health Sciences, SRI International, Menlo Park, California, USA.
Mov Disord. 2012 Jul;27(8):947-57. doi: 10.1002/mds.25028. Epub 2012 Jun 12.
Converging research efforts suggest that nicotine and other drugs that act at nicotinic acetylcholine receptors (nAChRs) may be beneficial in the management of Parkinson's disease. This idea initially stemmed from the results of epidemiological studies that demonstrated that smoking is associated with a decreased incidence of Parkinson's disease. The subsequent finding that nicotine administration protected against nigrostriatal damage in parkinsonian animal models led to the idea that nicotine in tobacco products may contribute to this apparent protective action. Nicotine most likely exerts its effects by interacting at nAChRs. Accumulating research indicates that multiple subtypes containing nAChRs, including α4β2, α6β2, and/or α7, may be involved. Stimulation of nAChRs initially activates various intracellular transduction pathways primarily via alterations in calcium signaling. Consequent adaptations in immune responsiveness and trophic factors may ultimately mediate nicotine's ability to reduce/halt the neuronal damage that arises in Parkinson's disease. In addition to a potential neuroprotective action, nicotine also has antidepressant properties and improves attention/cognition. Altogether, these findings suggest that nicotine and nAChR drugs represent promising therapeutic agents for the management of Parkinson's disease.
研究工作的成果表明，尼古丁和其他作用于烟碱型乙酰胆碱受体（nAChR）的药物可能有益于帕金森病的治疗。这一观点最初源于流行病学研究的结果，该研究表明吸烟与帕金森病的发病率降低有关。随后发现尼古丁给药可防止帕金森病动物模型中的黑质纹状体损伤，这导致了烟草产品中的尼古丁可能有助于这种明显的保护作用的观点。尼古丁很可能通过与 nAChR 相互作用来发挥其作用。越来越多的研究表明，包含 nAChR 的多种亚型，包括 α4β2、α6β2 和/或 α7，可能参与其中。nAChR 的刺激最初通过改变钙信号主要激活各种细胞内转导途径。随后免疫反应和营养因子的适应性可能最终介导尼古丁减少/阻止帕金森病中神经元损伤的能力。除了潜在的神经保护作用外，尼古丁还具有抗抑郁作用，并改善注意力/认知能力。总之，这些发现表明尼古丁和 nAChR 药物是治疗帕金森病的有前途的治疗剂。
