HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Clinical and molecular genetics of the phosphodiesterases (PDEs).

Abstract
Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis of cAMP and GMP. They are critical regulators of the intracellular concentrations of cAMP and cGMP as well as of their signaling pathways and downstream biological effects. PDEs have been exploited pharmacologically for more than half a century, and some of the most successful drugs worldwide today affect PDE function. Recently, mutations in PDE genes have been identified as causative of certain human genetic diseases; even more recently, functional variants of PDE genes have been suggested to play a potential role in predisposition to tumors and/or cancer, especially in cAMP-sensitive tissues. Mouse models have been developed that point to wide developmental effects of PDEs from heart function to reproduction, to tumors, and beyond. This review brings together knowledge from a variety of disciplines (biochemistry and pharmacology, oncology, endocrinology, and reproductive sciences) with emphasis on recent research on PDEs, how PDEs affect cAMP and cGMP signaling in health and disease, and what pharmacological exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in a way that prevents or treats certain human diseases.
AuthorsMonalisa F Azevedo, Fabio R Faucz, Eirini Bimpaki, Anelia Horvath, Isaac Levy, Rodrigo B de Alexandre, Faiyaz Ahmad, Vincent Manganiello, Constantine A Stratakis
JournalEndocrine reviews (Endocr Rev) Vol. 35 Issue 2 Pg. 195-233 (Apr 2014) ISSN: 1945-7189 [Electronic] United States
PMID24311737 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Cyclic GMP
Topics
  • Animals
  • Cyclic AMP (metabolism)
  • Cyclic GMP (metabolism)
  • Humans
  • Isoenzymes (genetics, metabolism)
  • Mice
  • Phosphodiesterase Inhibitors (pharmacology)
  • Phosphoric Diester Hydrolases (genetics, metabolism)
  • Signal Transduction (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: