Department of Integrated Traditional Chinese and Western Medicine, the General Hospital of Chinese People's Armed Police Forces , Beijing 100039, China.
Neurosci Bull. 2010 Feb;26(1):66-76. doi: 10.1007/s12264-010-0302-z.
Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.
帕金森病（PD）是由黑质致密部（SNpc）多巴胺（DA）神经元进行性退化引起的，导致纹状体中 DA 缺乏。因此，出现了运动迟缓、僵硬和震颤等症状。PD 神经元死亡的病因仍然不清楚。多巴胺能神经元退化的几个可能机制仍然难以捉摸。已经提出了 PD 中神经元退化的各种机制，包括自由基形成、氧化应激、线粒体功能障碍、兴奋性毒性、钙细胞毒性、营养因子缺乏、炎症过程、遗传因素、环境因素、一氧化氮的毒性作用和细胞凋亡。所有这些因素相互作用，导致毒性的恶性循环，导致神经元功能障碍、萎缩，最终导致细胞死亡。大量证据表明，自由基和氧化应激可能在 PD 的发病机制中起关键作用。然而，目前药物治疗不能完全治愈这种疾病。尽管左旋多巴（L-Dopa）替代疗法仍然是 PD 症状治疗的金标准，但只能缓解临床症状。此外，患者在接受 L-Dopa 治疗数年后通常会出现严重的副作用。到目前为止，还没有治疗方法可以阻止或至少减缓患者的神经退行性变。因此，不仅努力提高 L-Dopa 治疗 PD 的效果，而且还研究具有抗帕金森病和神经保护作用的新药。在这里，讨论了当前和未来 PD 治疗方法的优缺点。目前的治疗方法包括多巴胺能治疗、DA 激动剂、MAO-B 抑制剂、COMT 抑制剂、抗胆碱能药物、手术如苍白球切开术和更具体的苍白球内（GPi）或丘脑底核（STN）深部脑刺激，以及干细胞移植。
