PDE Inhibition and cognition enhancement

There has been an increasing interest in the development of phosphodiesterase (PDE) inhibitors for the treatment of cognitive dysfunctions. In this editorial, the mechanism of action of PDEs is briefly described, while the effects of different PDE inhibitors in preclinical models are reviewed. Based on the expression of PDE mRNA in the human brain, it is suggested that PDE1 and PDE10 inhibitors are strong candidates for the development of cognition enhancers. However, the complex nature of the expression of PDEs in the brain warrants further research into the role of PDEs in the signaling pathways in brain circuits. The development of PDE inhibitors, which are selective for PDE splicing isoforms, may be promising for future drug development.