Ask about this productRelated genes to: PDE4B antibody
- Gene:
- PDE4B NIH gene
- Name:
- phosphodiesterase 4B
- Previous symbol:
- DPDE4
- Synonyms:
- -
- Chromosome:
- 1p31.3
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-29
- Date modifiied:
- 2016-10-05
Related products to: PDE4B antibody
Related articles to: PDE4B antibody
- Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, has been extensively investigated for the treatment of pulmonary fibrosis; however, its therapeutic potential and mechanisms of action in idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) remain to be elucidated. - Source: PubMed
Publication date: 2026/05/07
Cui XiLi WenjunChai HuiJiang YiGuo JinYang JumeiZhu JiaruiZhang Sigong - Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal lung disease with a median survival of 3-5 years, driven by a profound unmet medical need. The current standard-of-care agents, pirfenidone and nintedanib, merely slow disease progression and are burdened by significant toxicity. This review synthesizes the basic, clinical, and translational evolution of novel pharmacological approaches for IPF, analyzing the critical lessons from recent high-profile clinical trial failures and successes. This review followed a narrative, analytical methodology, examining key Phase 2 and 3 clinical trials to identify a "failure-to-refinement" trajectory in drug development. Analysis reveals that targeting broad-spectrum enzymes (e.g., autotaxin via ziritaxestat) or downstream effectors (e.g., Connective Tissue Growth Factor (CTGF) via pamrevlumab) has failed, likely due to mechanistic redundancy or insufficient target engagement. In contrast, highly specific, next-generation inhibitors targeting upstream signal initiation points such as the lysophosphatidic acid receptor 1 (LPAR1) (admilparant) and local αv6 integrin-mediated activation of transforming growth factor-beta (TGF-β) (bexotegrast) have yielded promising Phase 2 data, demonstrating a sophisticated translational learning loop. Furthermore, the geroscience approach targeting cellular senescence (dasatinib/quercetin) has introduced a controversial new paradigm, while the recent approval of nerandomilast (a phosphodiesterase 4B (PDE4B) inhibitor) establishes a new therapeutic class. The IPF pipeline has matured, moving from broad attenuation toward specific, mechanism-based inhibition. This shift, informed by interpreting trial failures, is guiding the development of therapies toward disease modification and combination strategies, offering a tangible path toward curative-intent treatments. - Source: PubMed
Publication date: 2026/04/21
Mansour Ghaith KHajjar Ahmad WSukkarieh Hatouf H - Chronic psychosocial stress is a major precipitant of Major Depressive Disorder (MDD), yet the glial mechanisms that translate sustained stress into maladaptive myelin and immune changes remain unclear. Using chronic social defeat stress and single-nucleus RNA sequencing of anterior medial PFC (mPFC) oligodendroglia, we identified a mature-oligodendrocyte cluster almost exclusively from stress-susceptible animals, marked by immune genes (MHCII) and upregulated Pde4b. Integration with a human MDD single-nucleus RNA sequencing dataset confirmed a conserved immune-like oligodendrocyte (ImOL) subset coexpressing Plp1 and Cd74 and enriched for Pde4b. Mechanistically, PDE4 inhibition with crisaborole elevated cAMP-PKA-CREB signaling, blocked IFNγ-induced MHCII expression, and engaged the eIF2α-ATF4/CHOP arm of the integrated stress response (ISR). In vivo modulation of the ISR with ISRIB or guanabenz bidirectionally controlled ImOL prevalence and stress-related behaviors. These findings position Pde4b-cAMP-ISR signaling as a regulator of oligodendroglial immune phenotypes and a promising target to modulate myelination and neuroinflammation in stress-related disorders. - Source: PubMed
Publication date: 2026/05/05
Madeira Miguel MHage ZacharyKoliatsis DimitrisKokkosis Alexandros GNnah KimberlyRhee Alexander JRahme Gilbert JKamvisios KatherineKoromilas Antonis ERosati BarbaraMcKinnon DavidTsirka Stella E - Alcohol use disorder (AUD) is a complex polygenic disease. Rodent models of alcohol dependence have been instrumental in modeling various aspects of dependence. Single-nucleus transcriptomics has enabled the profiling of cell-type-specific changes in gene expression in both human AUD and animal models. In this study, we identified shared dysregulated transcriptomic networks (TN), comprising gene co-expression modules and gene regulatory networks (GRNs) in a mouse model of alcohol dependence and individuals with AUD. Through cell-type-specific TN analysis, we identified translationally relevant, conserved dependence dysregulated molecular signatures. We identified conserved dependence-upregulated gene co-expression modules in astrocytes and oligodendrocytes, with hub genes Slc1a3 and Pde4b, respectively. These genes are linked to alcohol dependence mechanisms, such as glutamate signaling, a well-established target of alcohol's effects, and PDE4, whose inhibition has been shown to reduce alcohol intake in preclinical and clinical studies. We then integrated publicly available human and mouse GRN data to identify upstream regulators of alcohol-dysregulated gene signatures in each cell type. This approach revealed a set of transcription factors (TFs), including Mef2a, Mef2c, Jund, Nr3c1, and Zeb1, that were upstream of most dysregulated genes in both the mouse and human datasets and have established relevance to addiction biology, representing promising targets for translational research. Collectively, these findings demonstrate the utility of cross-species, cell-type-specific network analysis for uncovering conserved molecular mechanisms in alcohol dependence. The identification of shared dysregulated networks, cell type homology, and upstream regulators provides a foundation for developing translationally relevant targeting strategies that can be tested in animal models. - Source: PubMed
Publication date: 2026/04/21
Salem NihalWarden AnnaRoberts AmandaRoberto MarisaMayfield R Dayne - The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is a robust, rapid-acting antidepressant whose molecular effects have not been fully elucidated. Phosphodiesterase-4 (PDE4), which terminates cyclic adenosine monophosphate (cAMP) activity, may underlie antidepressant response. In particular, previous studies found that whole brain binding of the positron emission tomography (PET) radioligand [C](R)-rolipram to PDE4 was decreased in individuals with major depressive disorder; eight weeks of antidepressant treatment rescued this decrease in [C](R)-rolipram binding. This study used [C](R)-rolipram, which targets all PDE4 subtypes, and [F]PF-06445974, which is preferential for PDE4B over PDE4D, to determine whether ketamine infusion could rapidly increase cAMP activity in rats (at 10 mg/kg) and rhesus macaques (at 0.5 mg/kg). Ketamine increased [C](R)-rolipram binding to PDE4 in rats (mean standardized uptake value (SUV) increase=24% ± 14%, range=3%-42%, p = 0.004) and in monkeys (mean distribution volume (V) increase=14% ± 2%, range=12%-16%, p = 0.003). Ketamine also increased [F]PF-06445974 binding in monkeys within one hour of infusion (mean V increase 28% ± 7%, range=16%-37%, p = 0.008). When [C](S)-rolipram, which has no specific binding to PDE4, was used to control for the effects of ketamine on blood flow and radioligand delivery in rats, no consistent effects were observed for ketamine. Collectively, the results suggest that ketamine infusion rapidly increases cAMP activity and may be an underlying mechanism for ketamine's rapid antidepressant effects. These data support a common pathway for cAMP and antidepressant action and suggest that PDE4 inhibition, particularly PDE4B, may be an effective and rapid-acting antidepressant mechanism. - Source: PubMed
Publication date: 2026/04/21
Parcon Paul ABardhoshi AmandaOlsen-Dufour AmandaCureton RavenJana SusovanMorse Cheryl LHenter Ioline DTotis JuliaJenson Adrian EPamie-George Matilah TLiow Jeih-SanZoghbi Sami SWu ShawnPike Victor WInnis Robert B