Role of Cyclic Nucleotide Phosphodiesterases in Inner Ear and Hearing

摘要

Cyclic Nucleotide Phosphodiesterase (PDE) comprise a family of 11 enzymes that hydrolyze cyclic nucleotides. PDEs aid in the regulation of secondary messengers, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP), through the degradation of phosphodiester bonds (Huang et al., 2010; Ahmad et al., 2015; Epstein, 2017). These secondary messengers, cAMP and cGMP, are vital components of various cell signaling pathways, making their regulation by PDEs important to numerous biological processes (Weber et al., 2017; Yarwood et al., 2017). The regulation of secondary messengers by phosphodiester bond degradation occurs when PDEs hydrolyze 3′,5′ cyclic nucleotides cAMP and cGMP to their inactive nucleoside 5′-monophosphate form (Tetsi et al., 2017). While PDE functions are generally well-understood and manipulated for treatment, there exists minimal information about their role in inner ear and implications on human hearing. Though current knowledge remains limited, understanding the role of PDEs in the inner ear holds a great potential to develop novel treatment modalities for hearing loss and decrease the prevalence of deafness caused by ototoxicity.