Molecular Morse Code: cAMP and cGMP Signaling in Health and Pathogenesis

Introduction: Cyclic nucleotides, particularly cyclic adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP), are widely regarded as pivotal second messengers involved in a wide array of physiological processes. These include gene transcription, signal transduction, vascular regulation, neuronal communication, energy homeostasis, cellular proliferation and adhesion. Methods: Relevant studies were retrieved through electronic searches of PubMed, Scopus, Web of Science, and Google Scholar. The search strategy combined terms such as “cAMP”, “cGMP”, or “cyclic nucleotide” with “neuroprotective”, “cardioprotective”, and “cancer”. Results: Recent studies have highlighted the critical role of cyclic nucleotide Phosphodiesterases (PDEs) in modulating these signalling pathways by shaping intracellular signalling microdomains and restricting the diffusion of cAMP and cGMP. Importantly, dysregulation of cyclic nucleotide signalling has been implicated in various pathological conditions. Discussion: The growing body of evidence underscores the significance of these messengers in maintaining normal cellular functions and reveals their involvement in the pathophysiology of diseases such as cardiovascular disorders, neurological diseases, cancers, and bone-related conditions. Targeting components of cyclic nucleotide signalling pathways, particularly PDEs, presents a promising therapeutic strategy. Conclusion: This review discusses the fundamental roles of cAMP and cGMP in cellular signalling, the regulatory functions of PDEs, and explores the potential of cyclic nucleotide signalling as a target for the development of innovative therapeutic interventions.