Elucidating the Signaling Pathways Involved in Erectile Dysfunction

Background: Erectile Dysfunction (ED) is a common sexual disorder among men aged 20 years and over. It is predominantly characterized by alterations in the key physiological pathways regulating erectile function, such as nitric oxide and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK). Beyond these pathways, multiple molecular signaling networks are involved in ED pathogenesis. Objective: This review aims to describe the major signal transduction pathways that impact erectile function and contribute to the introduction of the pathogenesis of ED. Methods: A literature review of ED was performed from 2000 to 2023 using PubMed, Scopus, and Embase. “ED” and “related signaling pathway”, “molecular mechanisms” terms were used. Results: Further basic and clinical studies are required to define the underlying molecular mechanisms of ED. The signaling pathways that were not affected by phosphodiesterase type 5 inhibitors (PDE5i) may be the reason for the reduced efficacy of this first-line treatment option in a variety of conditions. Conclusion: There is still a need for a deeper description of the molecular mechanisms in terms of fibrosis, angiogenesis, apoptosis, inflammation, oxidative stress, autophagy, and hypoxia to identify new possible targets underlying the pathogenesis of ED. This comprehensive review expounds on the principal signaling pathways, offering valuable insights that may catalyze the development of innovative and enhanced therapies for managing ED.