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左旋多巴治疗帕金森病的分子作用。

Molecular Effects of L-dopa Therapy in Parkinson's Disease.

机构信息

Laboratory of Neurobiology, Department of Neurology.

Department of Biochemistry and Molecular Biology.

出版信息

Curr Genomics. 2014 Feb;15(1):11-7. doi: 10.2174/1389202914666131210213042.

Abstract

Parkinson's disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early -60's of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and ab-sence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD pa-tients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2'-deoxyguanosine, apoptotic proteins) and in-flammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol com-pounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.

摘要

帕金森病(PD)是老年人中最常见的神经退行性疾病之一。发病的平均年龄为 55 岁,70 岁时患 PD 的风险增加 5 倍。在 PD 中,运动和非运动(NMS)功能均受损。PD 运动功能障碍治疗策略简单,通常基于通过 L-二羟基苯丙氨酸(L-dopa)和多巴胺(DA)激动剂增强多巴胺能传递。L-dopa 是 Hornykiewicz 在 20 世纪 60 年代早期发现的,用于治疗 PD 患者。L-dopa 治疗 PD 与纹状体神经递质(DA)水平降低以及脑内神经末梢 DA 转运体缺失有关。L-dopa 也可能间接刺激 D1 和 D2 家族的受体。给予 PD 患者 L-dopa,尤其是长期治疗,可能会导致毒性和炎症反应增加以及生物硫醇代谢紊乱等副作用。因此,建议对接受 L-dopa 治疗的 PD 患者进行氧化应激标志物(8-氧-2'-脱氧鸟苷、凋亡蛋白)和炎症因子(高敏 C 反应蛋白、可溶性细胞间黏附分子)以及生物硫醇化合物(同型半胱氨酸、半胱氨酸、谷胱甘肽)的监测。在 PD 的早期阶段,联合使用维生素 B6、B12 和叶酸以及有效的抗氧化剂和/或抗炎药物治疗,可能有助于改善 PD 患者的生活质量,并减缓或阻止疾病的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/3958954/008c1b0dedc0/CG-15-11_F1.jpg

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