title: Phosphodiesterases: Regulators of cyclic nucleotide signals and novel molecular target for movement disorders.
abstract: Movement disorders rank among the most common neurological disorders. During the last two decades substantial progress has been made in understanding of the pathological basis of these disorders. Although, several mechanisms have been proposed, downregulation of cyclic nucleotide mediated signaling cascade has consistently been shown to contribute to the striatal dysfunctioning as seen in movement disorders. Thus, counteracting dysregulated cyclic nucleotide signaling has been considered to be beneficial in movement disorders. Cyclic nucleotide phosphodiesterases (PDEs) are the enzymes responsible for the breakdown of cyclic nucleotides and upregulation in PDE activity has been reported in various movement disorders. Thus, PDE inhibition is considered to be a novel strategy to restore cerebral cyclic nucleotide levels and their downstream signalling cascade. Indeed, various PDE inhibitors have been tested pre-clinically and were reported to be neuroprotective in various neurodegenerative disorders associated with movement disabilities. In this review, we have discussed a putative role of PDE inhibitors in movement disorders and associated abnormalities.
authors.affiliation: Neuropharmacology Division, I S F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: Sorabh
authors.initials: S
authors.lastname: Sharma
authors.forename: Kushal
authors.initials: K
authors.lastname: Kumar
authors.forename: Rahul
authors.initials: R
authors.lastname: Deshmukh
authors.forename: Pyare Lal
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009069:Movement Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009712:Nucleotides, Cyclic; D010727:Phosphoric Diester Hydrolases
keywords: Cyclic nucleotides; Dyskinesia's; Huntington's disease; Movement disorders; Parkinson's disease; Phosphodiesterase inhibitors