Abstract：
Neurodegenerative diseases and brain tumours represent important health challenges due to their severe nature and debilitating consequences that require substantial medical care. Interestingly, these conditions share common physiological characteristics, namely increased glutamate, and adenosine transmission, which are often associated with cellular dysregulation and damage. Guanosine, an endogenous nucleoside, is safe and exerts neuroprotective effects in preclinical models of excitotoxicity, along with cytotoxic effects on tumour cells. However, the lack of well-defined mechanisms of action for guanosine hinders a comprehensive understanding of its physiological effects. In fact, the absence of specific receptors for guanosine impedes the development of structure-activity research programs to develop guanosine derivatives for therapeutic purposes. Alternatively, given its apparent interaction with the adenosinergic system, it is plausible that guanosine exerts its neuroprotective and anti-tumorigenic effects by modulating adenosine transmission through undisclosed mechanisms involving adenosine receptors, transporters, and purinergic metabolism. Here, several potential molecular mechanisms behind the protective actions of guanosine will be discussed. First, we explore its potential interaction with adenosine receptors (A1R and A2AR), including the A1R-A2AR heteromer. In addition, we consider the impact of guanosine on extracellular adenosine levels and the role of guanine-based purine-converting enzymes. Collectively, the diverse cellular functions of guanosine as neuroprotective and antiproliferative agent suggest a multimodal and complementary mechanism of action.
摘要：
神经退行性疾病和脑肿瘤由于其严重的性质和需要大量医疗护理的衰弱后果而代表了重要的健康挑战。有趣的是,这些情况具有共同的生理特征，即谷氨酸增加，和腺苷传递，通常与细胞失调和损伤有关。鸟苷,内源性核苷，是安全的，在兴奋性毒性的临床前模型中发挥神经保护作用，以及对肿瘤细胞的细胞毒性作用。然而,缺乏明确的鸟苷作用机制阻碍了对其生理作用的全面理解。事实上,鸟苷特异性受体的缺乏阻碍了开发用于治疗目的的鸟苷衍生物的结构活性研究计划的发展。或者，鉴于其与腺苷系统的明显相互作用，似乎鸟苷通过涉及腺苷受体的未公开机制调节腺苷传递来发挥其神经保护和抗肿瘤作用，运输商,和嘌呤能代谢。这里,将讨论鸟苷保护作用背后的几种潜在分子机制。首先,我们探索其与腺苷受体（A1R和A2AR）的潜在相互作用，包括A1R-A2AR异聚体。此外,我们考虑了鸟苷对细胞外腺苷水平的影响以及基于鸟嘌呤的嘌呤转化酶的作用.总的来说，鸟苷作为神经保护和抗增殖剂的多种细胞功能表明了多模式和互补的作用机制。
