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

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

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

Crisaborole, a boron-containing drug was approved by the FDA in 2016 for the treatment of atopic dermatitis, and as of 2024 is being commercialized by Pfizer under the name of Eucrisa (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) mainly acting on PDE4B. [10][11][12]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000184588 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 "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. ↑ "Eucrisa (crisaborole) Ointment". U.S. Food and Drug Administration (FDA). 23 January 2017. Retrieved 28 April 2020.
  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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