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嘌呤能信号在帕金森病中的作用:一个多靶点系统对抗神经退行性变。

Purinergic Signalling in Parkinson's Disease: A Multi-target System to Combat Neurodegeneration.

机构信息

Department of Neurology, Faculty of Medicine, Semmelweis University, Balassa u. 6., Budapest, 1083, Hungary.

Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43., Budapest, 1083, Hungary.

出版信息

Neurochem Res. 2019 Oct;44(10):2413-2422. doi: 10.1007/s11064-019-02798-1. Epub 2019 May 4.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons that results in characteristic motor and non-motor symptoms. L-3,4 dihydroxyphenylalanine (L-DOPA) is the gold standard therapy for the treatment of PD. However, long-term use of L-DOPA leads to side effects such as dyskinesias and motor fluctuation. Since purines have neurotransmitter and co-transmitter properties, the function of the purinergic system has been thoroughly studied in the nervous system. Adenosine and adenosine 5'-triphosphate (ATP) are modulators of dopaminergic neurotransmission, neuroinflammatory processes, oxidative stress, excitotoxicity and cell death via purinergic receptor subtypes. Aberrant purinergic receptor signalling can be either the cause or the result of numerous pathological conditions, including neurodegenerative disorders. Many data confirm the involvement of purinergic signalling pathways in PD. Modulation of purinergic receptor subtypes, the activity of ectonucleotidases and ATP transporters could be beneficial in the treatment of PD. We give a brief summary of the background of purinergic signalling focusing on its roles in PD. Possible targets for pharmacological treatment are highlighted.

摘要

帕金森病(PD)是第二常见的神经退行性疾病,其特征是多巴胺能神经元进行性丧失,导致特征性运动和非运动症状。L-3,4 二羟基苯丙氨酸(L-DOPA)是治疗 PD 的金标准疗法。然而,L-DOPA 的长期使用会导致运动障碍和运动波动等副作用。由于嘌呤具有神经递质和共递质特性,嘌呤能系统的功能在神经系统中得到了彻底研究。腺苷和三磷酸腺苷(ATP)通过嘌呤能受体亚型调节多巴胺能神经传递、神经炎症过程、氧化应激、兴奋性毒性和细胞死亡。嘌呤能受体信号传导异常既可以是许多病理状况的原因,也可以是其结果,包括神经退行性疾病。许多数据证实嘌呤能信号通路参与 PD。嘌呤能受体亚型的调节、外核苷酸酶的活性和 ATP 转运体的活性可能对 PD 的治疗有益。我们简要总结了嘌呤能信号的背景,重点介绍了其在 PD 中的作用。强调了可能的药物治疗靶点。

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