Phosphodiesterase 8 (PDE8), a novel target for neurodegenerative diseases.

Phosphodiesterases (PDEs) constitute a superfamily of enzymes comprising 11 distinct families that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby precisely regulating the spatiotemporal dynamics of intracellular cyclic nucleotides. Among these PDEs, PDE8 is distinguished by its high affinity and specificity for cAMP and exerts diverse biological effects. The PDE8 family comprises two genes, Pde8a and Pde8b, which are widely distributed throughout the brain and are expressed in both neuronal and glial cells. The widespread distribution of PDE8 in the brain suggests its involvement in roles of the central nervous system (CNS). In this context, dysregulation of PDE8 has been implicated in the pathogenesis of several CNS diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review aimed to enhance the understanding of the role of PDE8 in the mechanisms underlying neurodegenerative diseases, while providing a theoretical foundation and potential avenues for developing novel therapeutic strategies.