Ask about this productRelated genes to: PDE9A antibody
- Gene:
- PDE9A NIH gene
- Name:
- phosphodiesterase 9A
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 21q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-06-12
- Date modifiied:
- 2014-11-19
Related products to: PDE9A antibody
Related articles to: PDE9A antibody
- Oxidative stress and inflammation are key players in central nervous system (CNS) diseases and in neurodegeneration. In this field, the search for novel targets and therapeutic tools is wide open. In this study, the identification of potential inhibitors of phosphodiesterase 9 (PDE9), a target of growing interest in CNS diseases, was done by using a rational virtual screening approach that employed ligand- and structure-based methodologies. Furthermore, a novel method to evaluate PDE9A activity based on high-performance liquid chromatography (HPLC) was developed to address the need for a time- and cost-effective assay to evaluate inhibitors. One of the candidates identified by virtual screening demonstrated potent enzymatic inhibition, and subsequent in vitro tests proved its significant PDE9A-dependent anti-neuroinflammatory effects as it acted on pro-inflammatory mediators such as COX-2, IL-1β, TNFα, and IL-6. The results of this multidisciplinary study underscore the potential of developing PDE9A inhibitors to modulate cyclic guanosine monophosphate (cGMP) signaling pathways implicated in neuroinflammation and also potentially in synaptic plasticity and cognitive functions, paving the way for novel PDE9A-targeting inhibitors addressing neurodegenerative diseases. - Source: PubMed
Ribaudo GiovanniLanducci ElisaAnyanwu MargrateMazzantini CostanzaGiannangeli MatteoRosa StefanoMainolfi FrancescaCalvani MauraMemo MaurizioPellegrini-Giampietro Domenico EGianoncelli Alessandra - Alzheimer's disease (AD) is driven by genetic and epigenetic factors. A knowledge gap remains in applying DNA methylation (DNAm) to capture AD-specific signatures. We developed the AD DNA Methylation Index (AD-DMI), a brain-derived risk index constructed from 100 CpG sites identified by elastic-net logistic regression of methylation data from postmortem dorsolateral prefrontal cortex tissue. AD-DMI was evaluated in 722 older adults, including individuals with normal cognition (NC), mild cognitive impairment (MCI), and AD. AD-relevant associations were tested using generalized linear models, logistic regression, and path analyses, with applicable covariate adjustments. Higher AD-DMI scores were associated with lower global cognitive function, greater global AD neuropathologic burden, and increased odds of subjective memory complaints. AD-DMI predicted clinical diagnosis across the continuum, independent of cognition and pathology. Compared to the Cortical clock, AD-DMI showed stronger and more specific associations with both cognitive and pathological outcomes. Genes mapped to AD-DMI CpGs overlapped with eight genetic loci identified in AD genome-wide association studies, including , , and . AD-DMI was significantly associated with increased methylation at CpGs in , , and . AD-DMI provides a biologically grounded framework for linking disease-relevant methylation changes with cognitive and pathological outcomes in AD. - Source: PubMed
Publication date: 2026/04/29
Jiakponnah Nwanyieze NBiose Ifechukwude JFischer TracyCherry KatieCronin JamesJazwinski S MichalKim Sangkyu - The CCCTC-binding factor (CTCF) is a master regulator of topologically associating domains (TADs), which shape 3D genome architecture and gene regulation. While TAD evolution across species has been extensively studied, the evolution of CTCF binding sites (CBSs) in primates remains underexplored. Here, we employed a deep learning model to predict genome-wide CBSs in five primate species, including human, chimpanzee, gorilla, orangutan, and macaque. We found that approximately half of human CBSs are conserved across all five species. These primate-conserved CBSs cluster near TAD boundaries, exhibit stronger motif matches, and are subject to stronger selective constraints. In contrast, human-specific CBSs show signatures of positive selection. We identify a positively selected human-specific CBS that emerged de novo from ancestral noncoding sequence via three derived substitutions in the CTCF binding motif. This site anchors a TAD containing PDE9A, a gene involved in learning and memory, which exhibits strengthened enhancer-promoter interactions in humans relative to chimpanzees. Human-specific CBSs contribute to human-specific gene expression regulations, where nearby genes, such as PRDM16, ADCY1, and RIMS1, are differentially expressed and exhibit stronger or human-specific promoter-enhancer interactions in humans, compared to chimpanzees. We further demonstrate that distinct classes of transposable elements contribute differentially to conserved and human-specific CBSs. Moreover, genetic variants near human CBSs are more enriched for associations with complex traits and diseases. Our results highlight that natural selection has shaped CBS evolution in primates, driving both conservation and innovation in chromatin organization and contributing to human-specific regulatory evolution. - Source: PubMed
Zhu KangliZhuo JunjieZhen Ying - Heart failure with preserved ejection fraction (HFpEF) is a complex and increasingly prevalent cardiovascular disorder with limited effective therapeutic options. Dysregulation of cyclic guanosine monophosphate (cGMP) signaling has been implicated in its pathophysiology. Phosphodiesterase 9A (PDE9A), a cGMP-specific enzyme, has emerged as a potential therapeutic target due to its role in nitric oxide-independent signaling pathways associated with myocardial dysfunction. - Source: PubMed
Publication date: 2026/06/24
Lei XiaoyanWang RujieLi Yongmei - Phosphodiesterases (PDEs) are considered promising drug targets due to their close association with various pathological and physiological processes. We aimed to investigate the causal relationship between PDE inhibitors and hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR). - Source: PubMed
Publication date: 2026/05/20
Xia DandanLi SiyuLiu WenjieZhang YuhuiZhang ChenyingShe GuangtongWang Huiyan