神经退行性疾病和脑肿瘤因其严重的性质和需要大量医疗护理的令人衰弱的后果而代表着重要的健康挑战。有趣的是，这些病症具有共同的生理特征，即谷氨酸和腺苷传递增加，这通常与细胞失调和损伤有关。鸟苷是一种内源性核苷，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，并对肿瘤细胞具有细胞毒性作用。然而，鸟苷缺乏明确的作用机制阻碍了对其生理作用的全面了解。事实上，鸟苷特异性受体的缺乏阻碍了为治疗目的开发鸟苷衍生物的结构活性研究计划的发展。或者，考虑到鸟苷与腺苷能系统明显的相互作用，鸟苷可能通过涉及腺苷受体、转运蛋白和嘌呤能代谢的未公开机制调节腺苷传递，从而发挥其神经保护和抗肿瘤作用。在这里，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，我们还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，鸟苷作为神经保护剂和抗增殖剂的多种细胞功能表明了一种多模式和互补的作用机制。© 2024。作者获得 Springer Nature B.V. 的独家许可。

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.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.