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Adenosine signaling pathways as potential therapeutic targets in respiratory disease

机译：腺苷信号通路是呼吸系统疾病的潜在治疗靶标

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Introduction: Adenosine receptors (ARs) and their differential pattern of expression modulate a series of pleiotropic activities that are known to contribute to the control of inflammation, remodeling, and tissue repair. Consequently, pharmacological manipulation of adenosine signaling pathway is of great interest and is currently exploited as a therapeutic target for a number of respiratory diseases with several molecules with agonist and antagonist activities against known ARs being developed for the treatment of different conditions of the respiratory system. Areas covered: Herein, we will review the rational basis leading to the development of novel therapies for asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cystic fibrosis. Their most recent clinical development will be also discussed. Expert opinion: Advances in our understanding of the pathogenetic role of adenosine in respiratory diseases may be soon translated into effective treatment options. In consideration of the complex interplay driven by the different pattern of receptor distribution and/or affinity of the four known AR subtypes in specific cell types at different stages of the disease, it is likely that combination of selective antagonist/agonists for different AR subtypes will be required to obtain reasonable clinical efficacy. Alternatively, controlling the factors involved in driving adenosine concentrations in the tissue may be also of great significance.
机译：简介：腺苷受体（ARs）及其差异表达模式可调节一系列多效活性，这些活性有助于控制炎症，重塑和组织修复。因此，对腺苷信号传导途径的药理操作引起了极大的兴趣，并且目前被开发为许多呼吸道疾病的治疗靶标，具有针对已知AR的具有激动剂和拮抗剂活性的几种分子正在开发用于治疗呼吸系统的不同状况。涵盖的领域：在这里，我们将回顾导致哮喘，慢性阻塞性肺疾病（COPD），间质性肺疾病（ILD），肺动脉高压（PAH）和囊性纤维化新疗法发展的合理基础。他们的最新临床发展也将被讨论。专家意见：我们对腺苷在呼吸系统疾病中的致病作用的了解的进展可能很快会转化为有效的治疗选择。考虑到在疾病的不同阶段，由四种已知的AR亚型在特定细胞类型中的受体分布和/或亲和力的不同模式所驱动的复杂的相互作用，针对不同AR亚型的选择性拮抗剂/激动剂的组合可能会需要获得合理的临床疗效。或者，控制组织中驱动腺苷浓度的相关因素也可能具有重要意义。

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