Cyclic nucleotide phosphodiesterase (PDE)
enzymes catalyze the hydrolysis and inactivation of the
cyclic nucleotides cyclic
adenosine monophosphate and cyclic
guanosine monophosphate, which act as intracellular second messengers for many signal transduction pathways in the central nervous system. Several classes of PDE
enzymes with specific tissue distributions and
cyclic nucleotide selectivity are highly expressed in brain regions involved in cognitive and motor functions, which are known to be implicated in
neurodegenerative diseases, such as
Parkinson's disease and
Huntington's disease. The indication that
PDEs are intimately involved in the pathophysiology of different
movement disorders further stems from recent discoveries that mutations in genes encoding different
PDEs, including PDE2A, PDE8B, and PDE10A, are responsible for rare forms of monogenic
parkinsonism and
chorea. We here aim to provide a translational overview of the preclinical and clinical data on
PDEs, the role of which is emerging in the field of
movement disorders, offering a novel venue for a better understanding of their pathophysiology. Modulating
cyclic nucleotide signaling, by either acting on their synthesis or on their degradation, represents a promising area for development of novel therapeutic approaches. The study of PDE mutations linked to monogenic
movement disorders offers the opportunity of better understanding the role of
PDEs in disease pathogenesis, a necessary step to successfully benefit the treatment of both hyperkinetic and hypokinetic
movement disorders. © 2021 The Authors.
Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and
Movement Disorder Society.