The Emerging Role of Phosphodiesterases in Movement Disorders

Roberto Erro, Niccoló E. Mencacci, Kailash P. Bhatia*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2225-2243
Number of pages19
JournalMovement Disorders
Volume36
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • ADCY5
  • Huntington disease
  • PDE
  • adenylyl cyclases
  • cyclic nucleotides

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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