Oliveira-Giacomelli Ágatha, Naaldijk Yahaira, Sardá-Arroyo Laura, Gonçalves Maria C B, Corrêa-Velloso Juliana, Pillat Micheli M, de Souza Héllio D N, Ulrich Henning
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Department of Neurology and Neuroscience, Medical School, Federal University of São Paulo, São Paulo, Brazil.
Front Pharmacol. 2018 Apr 10;9:325. doi: 10.3389/fphar.2018.00325. eCollection 2018.
Since proving adenosine triphosphate (ATP) functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD), motor neuron diseases (MND), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's Disease (HD), restless leg syndrome (RLS), and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression. In neurodegenerative conditions, neural cell death provokes extensive ATP release and alters calcium signaling through purinergic receptor modulation. Consequently, neuroinflammatory responses, excitotoxicity and apoptosis are directly or indirectly induced. This review analyzes currently available data, which suggests involvement of the purinergic system in neuro-associated motor dysfunctions and underlying mechanisms. Possible targets for pharmacological interventions are also discussed.
自从证实三磷酸腺苷(ATP)在神经元/神经胶质细胞相互作用中作为神经递质发挥作用以来,嘌呤能系统在中枢神经系统范围内得到了更深入的研究。在伴有运动症状的神经系统疾病中,包括帕金森病(PD)、运动神经元病(MND)、多发性硬化症(MS)、肌萎缩侧索硬化症(ALS)、亨廷顿舞蹈病(HD)、不宁腿综合征(RLS)和共济失调,已注意到嘌呤能受体表达和活性的改变,表明该系统在疾病病因和进展中具有潜在作用。在神经退行性疾病中,神经细胞死亡会引发大量ATP释放,并通过嘌呤能受体调节改变钙信号传导。因此,会直接或间接诱导神经炎症反应、兴奋性毒性和细胞凋亡。本综述分析了现有数据,这些数据表明嘌呤能系统参与了与神经相关的运动功能障碍及其潜在机制。还讨论了药物干预的可能靶点。