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Treatment strategies for Parkinson’s disease

帕金森氏病的治疗策略

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Abstract

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.

摘要

帕金森氏病(Parkinson’s disease, PD)是由中脑黑质中多巴胺神经元变性, 导致纹状体系统多巴胺(DA)含量下降引起的神经病变。 其特征性症状包括震颤、 僵硬和运动徐缓等。 目前为止, 帕金森氏病神经元死亡的病因仍不清楚。 具体的神经变性机制包括自由基生成、 氧化应激、 线粒体异常、 兴奋性中毒、 钙中毒、 营养因子不足、 炎症过程、 一氧化氮毒性和细胞调亡。 这些因素相互增**形成恶性循环导致神经功能异常、 萎缩, 最终导致多巴胺神经元死亡。 大量实验提示在PD 病理过程中, 自由基的生成和氧化应激起关键作用。 目前, 药物疗法并不能治愈PD。 尽맜左旋多巴(L-Dopa)替代疗法一直是控制PD 症状的标准, 但其只能缓解临床症状, 并且L-Dopa 长期治疗会引起多种副作用。 目前尚无可行的疗法能遏制或减缓神经元变性。 因此, 研究不仅要致力于改善和延长L-Dopa对PD的治疗效果, 还要研发兼具抗PD与神经保护功能的药物。 本文综述了当前各种PD疗法的优缺点。 这些疗法包括DA 治疗、 DA 激动剂、 单胺氧化酶-B 抑制剂、 儿茶酚-O-甲基转移酶抑制剂、 抗谷氨酸药、 胆 碱能药物、 外科手术(深部大脑苍白球或丘脑术)和干细胞移植术等。 同时, 基于PD 病理过程, 对未来的药物神经保护作一展望。

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Authors and Affiliations

  1. Department of Integrated Traditional Chinese & Western Medicine, the General Hospital of Chinese People’s Armed Police Forces, Bei**g, 100039, China

    Hong Yuan  (袁红), Zhen-Wen Zhang  (张振文), Li-Wu Liang  (梁立武), Quan Shen  (沈权), **ang-Dang Wang  (王向党), Su-Mei Ren  (任素梅), Hong-Jie Ma  (马洪杰) & Shu-Jun Jiao  (焦淑军)

  2. Department of Immunology, Harbin Medical University, Harbin, 150086, China

    ** Liu  (刘**)

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  1. Hong Yuan  (袁红)
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Correspondence to Hong Yuan  (袁红).

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Yuan, H., Zhang, ZW., Liang, LW. et al. Treatment strategies for Parkinson’s disease. Neurosci. Bull. 26, 66–76 (2010). https://doi.org/10.1007/s12264-010-0302-z

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