Puchałowicz Kamila, Tarnowski Maciej, Baranowska-Bosiacka Irena, Chlubek Dariusz, Dziedziejko Violetta
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wielkopolskich Street, Szczecin 70-111, Poland.
Department of Physiology, Pomeranian Medical University, 72 Powstańców Wielkopolskich Street, Szczecin 70-111, Poland.
Int J Mol Sci. 2014 Dec 18;15(12):23672-704. doi: 10.3390/ijms151223672.
Purinergic signalling plays a crucial role in proper functioning of the nervous system. Mechanisms depending on extracellular nucleotides and their P2 receptors also underlie a number of nervous system dysfunctions. This review aims to present the role of purinergic signalling, with particular focus devoted to role of P2 family receptors, in epilepsy, depression, neuropathic pain, nervous system neoplasms, such as glioma and neuroblastoma, neurodegenerative diseases like Parkinson's disease, Alzheimer's disease and multiple sclerosis. The above-mentioned conditions are associated with changes in expression of extracellular ectonucleotidases, P2X and P2Y receptors in neurons and glial cells, as well as releasing considerable amounts of nucleotides from activated or damaged nervous tissue cells into the extracellular space, which contributes to disturbance in purinergic signalling. The numerous studies indicate a potential possibility of using synthetic agonists/antagonists of P2 receptors in treatment of selected nervous system diseases. This is of particular significance, since numerous available agents reveal a low effectiveness and often produce side effects.
嘌呤能信号传导在神经系统的正常功能中起着至关重要的作用。依赖细胞外核苷酸及其P2受体的机制也是许多神经系统功能障碍的基础。本综述旨在阐述嘌呤能信号传导的作用,特别关注P2家族受体在癫痫、抑郁症、神经性疼痛、神经系统肿瘤(如胶质瘤和神经母细胞瘤)、神经退行性疾病(如帕金森病、阿尔茨海默病和多发性硬化症)中的作用。上述疾病与神经元和神经胶质细胞中细胞外核苷酸酶、P2X和P2Y受体表达的变化有关,以及从活化或受损的神经组织细胞中释放大量核苷酸到细胞外空间,这导致嘌呤能信号传导紊乱。众多研究表明,使用P2受体的合成激动剂/拮抗剂治疗某些神经系统疾病具有潜在可能性。这具有特别重要的意义,因为许多现有药物疗效不佳且往往会产生副作用。