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<p> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年3月9日

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  • 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

摘要

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.