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腺苷受体亚型调节剂:对分子机制及其治疗应用的洞察

Adenosine receptor subtype modulators: Insight into molecular mechanisms and their therapeutic application.

作者信息

Solanki Nilay, Dodiya Rohinee, Vejpara Dhruvi, Azad Smruti, Patel Mehul, Patel Swayamprakash, Shah Umang, Soni Arun, Maheshwari Rajesh, Navale Archana, Patel Ashish, Patel Sandip, Sheth Devang, Tirgar Pravin, R Rachana

机构信息

Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus Changa 388421, Gujarat, India.

L.J. Instutite of Pharmacy, L.J. University Ahmedabad 382210, Gujarat, India.

出版信息

Am J Transl Res. 2025 Apr 15;17(4):2376-2395. doi: 10.62347/ZYVY9443. eCollection 2025.

Abstract

There are four different subtypes of adenosine receptors (ARs): A1, A2A, A2B, and A3. These receptors play a role in controlling healthy and unhealthy processes related to protecting neurons, inflammation, heart health, and the growth of cancer. The A1 receptors protect neurons and the heart, while the A2A receptors play a role in treating Parkinson's disease and cancer immunotherapy. Although much less abundant than A2A receptors, they are linked to asthma and diabetes, while the A3 receptors are promising targets for autoimmune diseases and cancer. Recent research has shown that agonists and antagonists that are specific to AR can be used as medicines by changing important biological pathways. A2A antagonists, A3 agonists, and other related compounds are being tested in people with heart failure, ischemia, neurodegenerative diseases, and inflammatory disorders. However, the main problem with this is the side effects, which include heart damage, low receptor selectivity, and drug responses that are specific to certain species. In the future, scientists need to find ways to make receptor-specific ligands that work better as medicines and have fewer side effects. Current advances include selective drugs for glaucoma, asthma, and oncology, as well as new approaches for neurodegenerative diseases and chronic inflammation. With these challenges addressed, AR therapies can transform the treatment landscape of complex conditions. This review covers the molecular mechanisms, tissue-specific roles, and translational progress of AR subtypes and further advocates for ongoing innovation to optimally tailor the clinical outcome of such interventions. Therefore, unlocking the full therapeutic potential of changing the AR could lead to new ways of treating a wide range of short-term and long-term illnesses.

摘要

腺苷受体(ARs)有四种不同的亚型:A1、A2A、A2B和A3。这些受体在控制与保护神经元、炎症、心脏健康和癌症生长相关的健康和不健康过程中发挥作用。A1受体保护神经元和心脏,而A2A受体在治疗帕金森病和癌症免疫疗法中发挥作用。虽然它们的数量比A2A受体少得多,但与哮喘和糖尿病有关,而A3受体是自身免疫性疾病和癌症的有前景的靶点。最近的研究表明,AR特异性的激动剂和拮抗剂可以通过改变重要的生物途径用作药物。A2A拮抗剂、A3激动剂和其他相关化合物正在心力衰竭、缺血、神经退行性疾病和炎症性疾病患者中进行测试。然而,这主要的问题是副作用,包括心脏损伤、受体选择性低以及特定物种的药物反应。未来,科学家需要找到方法来制造受体特异性配体,使其作为药物效果更好且副作用更少。目前的进展包括用于青光眼、哮喘和肿瘤学的选择性药物,以及针对神经退行性疾病和慢性炎症的新方法。解决这些挑战后,AR疗法可以改变复杂病症的治疗格局。本综述涵盖了AR亚型的分子机制、组织特异性作用和转化进展,并进一步倡导持续创新,以优化此类干预措施的临床结果。因此,释放改变AR的全部治疗潜力可能会带来治疗各种短期和长期疾病的新方法。

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