From purines to purinergic signalling: molecular functions and human diseases

This study is about Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as “purinergic signalling”. Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential.

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Fig: The causative role of purinergic signalling in human diseases. Purinoceptors, including P1, P2X and P2Y receptors, are diffusely expressed in every human body part, such as the nervous system, circulatory system, respiratory system, immune system, urinary system and others. Dysregulation of purinoceptors function leads to various diseases, including neurological, rheumatic, cardiovascular, cancer diseases and so on

Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

Huang, Z., Xie, N., Illes, P. et al. From purines to purinergic signalling: molecular functions and human diseases. Sig Transduct Target Ther6, 162 (2021). https://doi.org/10.1038/s41392-021-00553-z

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