Tasca Carla I, Lanznaster Débora, Oliveira Karen A, Fernández-Dueñas Victor, Ciruela Francisco
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Front Cell Neurosci. 2018 Oct 23;12:376. doi: 10.3389/fncel.2018.00376. eCollection 2018.
The function of guanine-based purines (GBPs) is mostly attributed to the intracellular modulation of heteromeric and monomeric G proteins. However, extracellular effects of guanine derivatives have also been recognized. Thus, in the central nervous system (CNS), a guanine-based purinergic system that exerts neuromodulator effects, has been postulated. The thesis that GBPs are neuromodulators emerged from and studies, in which neurotrophic and neuroprotective effects of these kinds of molecules (i.e., guanosine) were demonstrated. GBPs induce several important biological effects in rodent models and have been shown to reduce seizures and pain, stabilize mood disorder behavior and protect against gliomas and diseases related with aging, such as ischemia or Parkinson and Alzheimer diseases. studies to evaluate the protective and trophic effects of guanosine, and of the nitrogenous base guanine, have been fundamental for understanding the mechanisms of action of GBPs, as well as the signaling pathways involved in their biological roles. Conversely, although selective binding sites for guanosine have been identified in the rat brain, GBP receptors have not been still described. In addition, GBP neuromodulation may depend on the capacity of GBPs to interact with well-known membrane proteins in glutamatergic and adenosinergic systems. Overall, in this review article, we present up-to-date GBP biology, focusing mainly on the mechanisms of action that may lead to the neuromodulator role of GBPs observed in neurological disorders.
基于鸟嘌呤的嘌呤（GBP）的功能主要归因于异源三聚体和单体G蛋白的细胞内调节。然而，鸟嘌呤衍生物的细胞外作用也已得到认可。因此，在中枢神经系统（CNS）中，已推测存在一种发挥神经调节作用的基于鸟嘌呤的嘌呤能系统。GBP是神经调节剂这一论点源于[具体文献1]和[具体文献2]的研究，其中证明了这类分子（即鸟苷）的神经营养和神经保护作用。GBP在啮齿动物模型中诱导了几种重要的生物学效应，并且已显示出可减少癫痫发作和疼痛、稳定情绪障碍行为以及预防胶质瘤和与衰老相关的疾病，如缺血、帕金森病和阿尔茨海默病。评估鸟苷以及含氮碱基鸟嘌呤的保护和营养作用的[相关]研究，对于理解GBP的作用机制以及其生物学作用所涉及的信号通路至关重要。相反，尽管在大鼠脑中已鉴定出鸟苷的选择性结合位点，但GBP受体仍未被描述。此外，GBP神经调节可能取决于GBP与谷氨酸能和腺苷能系统中知名膜蛋白相互作用的能力。总体而言，在这篇综述文章中，我们介绍了最新的GBP生物学，主要关注可能导致在神经疾病中观察到的GBP神经调节作用的作用机制。
