PDE4B

cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene.[5]

PDE4B
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesPDE4B, DPDE4, PDEIVB, phosphodiesterase 4B
External IDsOMIM: 600127 MGI: 99557 HomoloGene: 1953 GeneCards: PDE4B
Orthologs
SpeciesHumanMouse
Entrez

5142

18578

Ensembl

ENSG00000184588

ENSMUSG00000028525

UniProt

Q07343

n/a

RefSeq (mRNA)
RefSeq (protein)

n/a

Location (UCSC)Chr 1: 65.79 – 66.37 MbChr 4: 101.94 – 102.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[5][6]

Clinical relevance

Altered activity of this protein has been associated with schizophrenia and bipolar disorder.[5] PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram.[7] PDE4B is involved in dopamine-associated and stress-related behaviours.[8] It has also recently been found to modulate cognition, as reduction in PDE4B activity improves memory and long-term plasticity in mouse models, possibly supporting further therapeutic applications.[9]

Inhibitors

AN2728, a boron-containing drug candidate that as of 2015 was under development by Anacor Pharmaceuticals for the topical treatment of psoriasis and atopic dermatitis (atopic eczema).[10][11][12] mainly acting on PDE4B.[12]

References
  1. GRCh38: Ensembl release 89: ENSG00000184588 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000028525 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)".
  6. Swerdlow, Neal R. (2010-08-19). Behavioral Neurobiology of Schizophrenia and Its Treatment. Springer Science & Business Media. ISBN 9783642137174.
  7. Porteous DJ, Millar JK, Brandon NJ, Sawa A (Dec 2011). "DISC1 at 10: connecting psychiatric genetics and neuroscience". Trends in Molecular Medicine. 17 (12): 699–706. doi:10.1016/j.molmed.2011.09.002. PMC 3253483. PMID 22015021.
  8. Francis, SH; Conti, M; Houslay, MD, eds. (2011). Phosphodiesterases as Drug Targets (PDF). Handbook of Experimental Pharmacology. Vol. 204. Springer Berlin Heidelberg. doi:10.1007/978-3-642-17969-3. ISBN 978-3-642-17968-6.
  9. "Scientists researching brain disorders create super-clever mice | NewsDaily". Archived from the original on 2015-08-20. Retrieved 2015-08-21.
  10. Anacor AN2728 at Anacor website Page accessed May 15, 2015
  11. Nazarian R, Weinberg JM (Nov 2009). "AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis". Current Opinion in Investigational Drugs. 10 (11): 1236–42. PMID 19876791.
  12. Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology". Dermatol. Online J. 20 (5): 22608. doi:10.5070/D3205022608. PMID 24852768.

Further reading
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