Instituto Cajal (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain ; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain ; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
Parkinsons Dis. 2013;2013:308052. doi: 10.1155/2013/308052. Epub 2013 Feb 7.
Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles.
帕金森病(PD)是一种主要影响老年人的神经退行性疾病。该病的病因尚不清楚,但年龄和环境因素起着重要作用。尽管已经描述了十几种与家族性帕金森病相关的基因突变,但遗传异常只能解释不到 10%的病例。帕金森病的分子基础是由于黑质中多巴胺能神经元的退化,导致基底神经节(尾状核/壳核)中多巴胺的丧失,从而导致疾病的运动障碍。甲基苯丙胺是世界上第二大广泛使用的非法药物。在啮齿动物中,甲基苯丙胺暴露会损害黑质中的多巴胺能神经元,导致纹状体中多巴胺的大量丧失。对人类甲基苯丙胺使用者的生化和神经影像学研究表明,纹状体和大脑其他区域的多巴胺和多巴胺转运体水平降低,以及明显的小胶质细胞激活,这些变化与 PD 患者观察到的变化相似。与这些相似之处一致,最近的流行病学研究表明,尽管甲基苯丙胺滥用和 PD 具有不同的症状特征,但甲基苯丙胺使用者患 PD 的可能性几乎是不使用者的两倍。