Lanznaster Débora, Dal-Cim Tharine, Piermartiri Tetsadê C B, Tasca Carla I
2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil; 3CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.
1Departamento de Bioquímica,; 2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil.
Aging Dis. 2016 Oct 1;7(5):657-679. doi: 10.14336/AD.2016.0208. eCollection 2016 Oct.
Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's and Alzheimer's diseases. The present review describes the findings of and studies and offers an update of guanosine effects in the CNS. We address the protein targets for guanosine action and its interaction with glutamatergic and adenosinergic systems and with calcium-activated potassium channels. We also discuss the intracellular mechanisms modulated by guanosine preventing oxidative damage, mitochondrial dysfunction, inflammatory burden and modulation of glutamate transport. New and exciting avenues for future investigation into the protective effects of guanosine include characterization of a selective guanosine receptor. A better understanding of the neuromodulatory action of guanosine will allow the development of therapeutic approach to brain diseases.
鸟苷是一种嘌呤核苷，在细胞代谢中具有重要功能，对退行性疾病或损伤具有保护作用。在过去十年中，在确定鸟苷在中枢神经系统（CNS）中的细胞外作用的调节作用方面取得了重大进展。来自啮齿动物和细胞模型的证据表明，鸟苷具有多种神经营养和神经保护作用，可预防癫痫发作、脊髓损伤、疼痛、情绪障碍以及与衰老相关疾病（如缺血、帕金森病和阿尔茨海默病）的有害后果。本综述描述了[具体研究1]和[具体研究2]的研究结果，并提供了鸟苷在中枢神经系统中作用的最新情况。我们阐述了鸟苷作用的蛋白质靶点及其与谷氨酸能和腺苷能系统以及钙激活钾通道的相互作用。我们还讨论了鸟苷调节的细胞内机制，这些机制可预防氧化损伤、线粒体功能障碍、炎症负担以及谷氨酸转运的调节。未来对鸟苷保护作用进行研究的新的、令人兴奋的途径包括对选择性鸟苷受体的表征。更好地理解鸟苷的神经调节作用将有助于开发针对脑部疾病的治疗方法。
