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

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.

Keywords: Adenosine receptors; G-protein coupling; cancer; clinical study; inflammation; neurodegeneration; preclinical.

Figure 1

Mechanism of Adenosine receptors [7].

Figure 2

Role of A1AR in different diseases.

Figure 3

Role of A2AR in different diseases.

Figure 4

Role of A3AR in different diseases.