The potential role of adenosinergic pathway and methylxanthines in Parkinson's disease: Blowing in the wind or not.

IF 2.5 4区医学 Q2 NEUROSCIENCES

Purinergic Signalling Pub Date : 2026-03-09 DOI:10.1007/s11302-025-10114-6

Alaa Ismail, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Luay M Alkazmi, Abdullah Faisal Albukhari, Mustafa M Shokr, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha

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引用次数: 0

Abstract

Parkinson's disease (PD) is a systemic neurodegenerative disease, and is mainly related to the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Despite extensive research regarding PD neuropathology, there are no active drugs to avert this disease. It has been described that the adenosine pathway, which is expressed centrally and peripherally, is involved in the pathogenesis of PD and other neurodegenerative diseases. Adenosine acts on adenosine receptors (ARs), including A1R, A2AR, A2BR, and A3R. Both A1R and A3R are neuroprotective, while A2AR and A2BR are neurotoxic for the brain. A2AR, in the SNpc, mediates the neurotoxicity of adenosine in PD. In addition, data from epidemiological studies highlighted controversial findings in PD and other neurodegenerative diseases. Therefore, the present review aims to revise from published articles the potential role of the adenosine pathway in PD neuropathology, and how methylxanthines affect the dopaminergic neurotransmission in the SNpc. This review highlighted that selective A2AR antagonists could be more effective than non-selective AR antagonists in the management of motor and non-motor symptoms of PD.

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腺苷能通路和甲基黄嘌呤在帕金森病中的潜在作用：是否在风中吹。

帕金森病（PD）是一种全身性神经退行性疾病，主要与黑质致密部（SNpc）多巴胺能神经元进行性变性有关。尽管对PD神经病理学进行了广泛的研究，但没有有效的药物来避免这种疾病。已有研究表明，腺苷途径在中枢和外周表达，参与PD和其他神经退行性疾病的发病机制。腺苷作用于腺苷受体（ARs），包括A1R、A2AR、A2BR和A3R。A1R和A3R都具有神经保护作用，而A2AR和A2BR对大脑具有神经毒性。SNpc中的A2AR介导PD中腺苷的神经毒性。此外，来自流行病学研究的数据强调了PD和其他神经退行性疾病中有争议的发现。因此，本综述旨在从已发表的文章中对腺苷途径在PD神经病理中的潜在作用以及甲基黄嘌呤如何影响SNpc中多巴胺能神经传递进行修订。这篇综述强调，选择性A2AR拮抗剂在治疗PD的运动和非运动症状方面可能比非选择性AR拮抗剂更有效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.