The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation.
The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation.
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DOI：
10.3389/fphar.2016.00158
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发表时间：
2016
影响因子：
5.6
通讯作者：
Belluardo N
中科院分区：
文献类型：
--
作者：
Di Liberto V;Mudò G;Garozzo R;Frinchi M;Fernandez-Dueñas V;Di Iorio P;Ciccarelli R;Caciagli F;Condorelli DF;Ciruela F;Belluardo N
鸟嘌呤嘌呤（GBP）不仅是代谢因子，而且是调节中枢神经系统重要功能的细胞外信号分子。因此，GBP介导的神经保护、行为反应和神经元可塑性已在文献中广泛描述。然而，虽然这些功能中的一些（即，GBP依赖性效应（GBP的神经营养效应）已经得到了很好的证实，但这些GBP依赖性效应背后的分子机制仍然未知。此外，到目前为止还没有描述GBP的质膜受体，因此GBP仍然被认为是孤儿神经调质。有趣的是，最近已经描述了GBP效应和腺苷受体活性之间的复杂和有争议的功能相互作用，从而引发了GBP作用机制可能以某种方式涉及腺苷受体的假设。在这里，我们回顾最近的数据描述GBP在大脑中的作用。我们专注于参与GBP调节神经元的可塑性，并在新的假设的基础上假定GBP受体。总的来说，我们期望揭示GBP世界的一些光，因为虽然这些分子可能代表某些神经系统疾病管理的优秀候选者，但缺乏推定的GBP受体排除了任何高通量筛选意图，以寻找有效的基于GBP的药物。
Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs.