cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. The PDE4D gene is complex and has at least 9 different isoforms that encode functional proteins.

We show that expression of PDE4D isoforms is consistently altered in primary human prostate cancer compared to benign tissue, with PDE4D7 being up-regulated while PDE4D5 and PDE4D9 are down-regulated.

Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play a fundamental role in cognitive, learning and memory consolidation processes and cancer development.

Jan 1, 2021 · Pharmacological phosphodiesterase 4D (PDE4D) inhibition shows therapeutic potential to restore memory function in Alzheimer’s disease (AD), but will likely evoke adverse side effects. As PDE4D encodes multiple isoforms, targeting specific isoforms may improve treatment efficacy and safety.

PDE4D long isoform is considered the best target for cognition improvement. PDE4D UCR2 carries a key residue, Phe196 that is nonconserved and could be, therefore, exploited to induce isoform specificity (Tyr274 in PDE4B).

Isoform-selective inhibition of PDE4 remains an obstacle, as clinically approved small molecules, including roflumilast, apremilast, and crisaborole, rely on binding the catalytic pocket of cAMP hydrolysis, which is highly conserved across isoforms within each PDE4 subfamily.

Jan 1, 2010 · We show that PDE4D allosteric modulators are potent in cellular and in vivo assays and have greatly reduced potential for emesis. Each PDE4 gene has multiple transcription units resulting in...

PDE4, is a cAMP-specific PDE and the largest PDE subfamily with over 35 different isoforms and as such, the most widely characterized PDE isoenzyme. It is the predominant isoenzyme in the majority of inflammatory cells, and the airways smooth muscle and is implicated in inflammatory airways disease.

Mar 30, 2025 · PDE4D (Phosphodiesterase 4D) is a Protein Coding gene. Diseases associated with PDE4D include Acrodysostosis 2 With Or Without Hormone Resistance and Acrodysostosis. Among its related pathways are GPCR downstream signalling and Response of …

Jun 12, 2023 · Here, we report the upregulation of specific PDE4D isoforms in transgenic AD mice and hippocampal neurons exposed to amyloid-β. Furthermore, by means of pharmacological inhibition and CRISPR-Cas9 knockdown, we show that the long-form PDE4D3, -D5, -D7, and -D9 isoforms regulate neuronal plasticity and convey resilience against amyloid-β in vitro.