Adenosine as a Multi-Signalling Guardian Angel in Human Diseases: When, Where and How Does it Exert its Protective Effects?

The importance of adenosine for human health cannot be overstated. Indeed, this ubiquitous nucleoside is an integral component of ATP, and regulates the function of every tissue and organ in the body. Acting via receptor-dependent and -independent mechanisms [the former mediated via four G-protein-coupled receptors (GPCRs), A1, A2A, A2B, and A3,], it has a significant role in protecting against cell damage in areas of increased tissue metabolism, and combating organ dysfunction in numerous pathological states. Accordingly, raised levels of adenosine have been demonstrated in epilepsy, ischaemia, pain, inflammation, and cancer, in which its behaviour can be likened to that of a guardian angel, even though there are instances in which overproduction of adenosine is pathological. In this review, we condense the current body of knowledge on the issue, highlighting when, where, and how adenosine exerts its protective effects in both the brain and the periphery.

TrendsAdenosine is a ubiquitous nucleoside, an integral part of ATP that acts as a homeostatic regulator through the activation of four GPCRs, A1, A2A, A2B, and A3, and through receptor-independent mechanisms.Adenosine levels increase in areas of inflammation and hypoxia, where it protects tissues by restoring the oxygen supply:demand ratio, as well as affecting preconditioning, exerting anti-inflammatory effects, and stimulating angiogenesis.Adenosine favours the resolution of pathologies such as epilepsy, pain, ischaemia, inflammation, and cancer, in which it behaves like a guardian angel against cellular damage.New adenosinergic drugs for pain, inflammatory diseases, and cancer are already in clinical development.