Phosphodiesterases or PDEs are a multigenic enzyme superfamily that is ubiquitously distributed in mammalians and is involved in intracellular signaling. The PDE superfamily is comprised of 21 genes that are represented by more than 100 mRNA products due to alternative splicing. The various PDE proteins specifically control the intracellular levels of cAMP and cGMP and regulate the localization, duration, and amplitude of the cyclic nucleotide signal.
PDEs represent important therapeutic targets in the treatment of various diseases including inflammation, cardiovascular disease and neurological disorders like dementia as well as erectile dysfunction. Among the various PDE family members, PDE3, PDE4 and PDE5 have been exploited as therapeutic targets with the successful development of at least 7 drugs.
Overexpression of PDE isoforms and impaired cAMP and/or cGMP generation has also been described in various cancer pathologies. Inhibition of selective PDE isoforms, which raises the levels of intracellular cAMP and/or cGMP, induces apoptosis and cell cycle arrest in a broad spectrum of tumour cells and regulates the tumour microenvironment.
PDE inhibitors can act as broad-spectrum neuroprotective agents acting through modulation of cell cycle elements and may display novel mode of action in Neurobiology science. PDEs are involved in various pathogenic mechanisms that lead to Alzheimer's disease (AD) which includes neuronal apoptosis, neurovascular dysfunction, neurotransmitter modulation, and impairment of neurogenesis.
SignalChem offers a diverse and comprehensive range of active PDEs and these can be tested using cAMP and/or cGMP as substrate.