Ask about this productRelated genes to: HDAC2 Blocking Peptide
- Gene:
- HDAC2 NIH gene
- Name:
- histone deacetylase 2
- Previous symbol:
- -
- Synonyms:
- RPD3, YAF1, KDAC2
- Chromosome:
- 6q21
- Locus Type:
- gene with protein product
- Date approved:
- 1996-11-15
- Date modifiied:
- 2019-02-19
Related products to: HDAC2 Blocking Peptide
Related articles to: HDAC2 Blocking Peptide
- The continuous failure to account for biological sex is a key impediment to developing effective neuroprotective treatments for ischemic stroke. While epigenetic modulators such as HDAC inhibitors show promise, the mechanisms behind their sexually dimorphic effects are unknown. We present a unique, sex-specific mechanism in which HDAC2 suppression offers substantial resilience to ischemic brain injury by significantly increasing the endogenous oxytocin (OXT) signaling axis. Through integrated in vitro and in vivo models, we show that HDAC2 knockdown not only reduces infarct size and enhances functional recovery, but also does so more effectively in females. We attribute this improved protection to a strong, female-specific increase of OXT and its receptor (OTR). This increased OXT signaling, possibly mediated by estrogen, resulted in significant decreases in apoptosis, neuroinflammation, and oxidative stress. Our findings show that HDAC2 serves as a critical epigenetic brake on a built-in neuroprotective mechanism that, when activated, triggers a therapeutically potent, sex-divergent response. This study sheds light on chemical biology by identifying a druggable epigenetic target that modulates an important neurohormonal circuit. More broadly, it establishes a new paradigm for individualized stroke therapy, shifting away from a one-size-fits-all strategy and toward leveraging innate, sex-specific protective mechanisms to improve treatment efficacy. - Source: PubMed
Publication date: 2026/03/25
Amin NashwaYuan XiaShi ZongjieWu FeiAbbasi Irum NazYang YangYe SuhongYang QiningGeng YuFang Marong - Cellular senescence plays a significant role in age-related conditions like osteoarthritis (OA) and intervertebral disc degeneration, in part due to the accumulation of senescent cells (SCs) in musculoskeletal tissues. Identifying novel therapeutics that can clear SCs is crucial for improving musculoskeletal health in the elderly. The present study aimed to elucidate the changes in Class I histone deacetylases (HDACs) and their role during senescence. All Class I HDACs except HDAC1 were downregulated during senescence in the human TC28a2 immortalized human chondrocyte cell line. Knockdown experiments showed that HDAC1 is essential for maintaining the viability of both non-senescent cells (NSCs) and SCs, while HDAC2 plays a key role in modulating inflammation in part by targeting the NF-κB signaling pathway. Mocetinostat, an HDAC inhibitor, selectively kills senescent TC28a2 cells and primary human knee chondrocytes via apoptosis while not affecting the viability of NSCs. Mocetinostat also affected both inflammation-associated and chondrogenesis-associated genes. Overall, our findings demonstrate a key role of Class I HDACs in regulating chondrocyte survival and ECM gene expression. Mocetinostat holds promise as a senolytic therapeutic for OA and potentially other aging-related musculoskeletal disorders. - Source: PubMed
Publication date: 2026/04/25
Gupta KavyaSwahn HannahLotz Martin K - The absence of the protein dystrophin in Duchenne muscular dystrophy (DMD) leads to progressive muscle weakness, failing regeneration and deregulation of nitric oxide (NO) signalling. We focused on L-citrulline, a precursor of L-arginine, required for NO production in muscle, which is reduced in dystrophic mdx muscle. - Source: PubMed
Publication date: 2026/04/22
Tulimiero LisamauraBoccanegra BrigidaMantuano PaolaMele AntoniettaDe Bellis MichelaLenti RobertaSanarica FrancescaCirmi SantaConte ElenaCappellari OrnellaSherrard Amber EGreen ArdawnaSrinivasa MiraFiorotto Marta LDe Luca Annamaria - Loss of Dot1l in Aquaporin 2 progenitor cell (AP)-derived distal renal segments in Dot1lAqp2cre (Dot1l) promotes kidney fibrosis by upregulating endothelin 1 (ET1) through histone deacetylase 2 (HDAC2), defining a Dot1l-HDAC2-ET1 profibrotic pathway. Additionally, Lcn2 was also upregulated in Dot1l mice. Here, we investigated whether and how Lipocalin 2 (Lcn2) contributes to this pathway. We performed in vivo studies using multiple mouse models with targeted deletion of Dot1l, Lcn2, or Edn1 in distal nephron segments or globally. Human CKD RNA-seq data analysis and in vitro studies in IMCD3 cells were conducted to validate the in vivo results. Because Lcn2 mice are available and Lcn2 is barely detectable in IMCD3 cells, Lcn2 down- and upregulation experiments were performed in mice and IMCD3 cells, respectively. Several approaches, including immunofluorescence staining and in situ hybridization, were employed to identify and confirm the Lcn2 profibrotic role. Both Dot1l deletion in AP in Dot1l mice and Dot1l silencing in IMCD3 cells upregulated Lcn2. Global deletion of Lcn2 in Dot1l mice attenuated HDAC2 and ET1 levels and reduced kidney fibrosis, establishing Lcn2 as a downstream effector of Dot1l-deletion-induced kidney fibrosis. Although conditional knockout of Edn1 in Dot1l mice showed Lcn2 expression comparable to that in Dot1l mice, they exhibited reduced kidney fibrosis, suggesting that Lcn2 lies upstream of ET1-mediated injury. Reanalysis of a human chronic kidney disease (CKD) dataset revealed that downregulation of DOT1L was coupled with upregulation of LCN2, HDAC2, and ET1, recapitulating our findings in Dot1l mice. These results were further validated in IMCD3 cells, in which Lcn2 was upregulated by Dot1l silencing, and addition of 293 T cells-secreted or recombinant Lcn2 led to increased HDAC2 and ET1 expression. Loss of Dot1l in AP upregulates Lcn2, which promotes kidney fibrosis by increasing HDAC2 and ET1. Our findings add Lcn2 as a new component to define a more complicated Dot1l-Lcn2-HDAC2-ET1 pro-fibrotic pathway that links AP-derived distal renal segments to kidney fibrosis. - Source: PubMed
Tsilosani AkakiGao ChaoMulroy EvelynPirzada NoorShehzad SanaDas ShreyaSun WeiChen EnuoGuo SunnyKnowles NicoleSajjad FizzaZhang Wenzheng - Kratom (Mitragyna speciosa) is a traditional Southeast Asian botanical long used for alleviating pain and boosting energy. Its chief bioactive compound, mitragynine (MG), exhibits both opioid-like and stimulant properties and has prompted interest in its potential role in pain management and opioid withdrawal support. However, its safety profile and underlying mechanisms remain incompletely understood. This systematic review critically synthesizes preclinical evidence on kratom's molecular, pharmacological, and epigenetic effects. Guided by PRISMA 2020 criteria, studies indexed in Scopus and Web of Science (2000-2024) were analyzed, focusing on receptor activity, intracellular signaling, and gene regulation in in vitro and in vivo models. Among 20 eligible studies, key findings indicate that kratom alkaloids engage μ-opioid, adrenergic, and serotonergic receptors; modulate dopaminergic and glutamatergic systems; and exert anti-inflammatory and analgesic effects. Under chronic exposure followed by withdrawal, MG was associated with reduced histone acetylation and increased HDAC2 expression, while Rab35 emerged as a potential withdrawal-associated biomarker. MG also inhibited cardiac ion channels and altered CYP450 enzyme expression, highlighting safety concerns related to cardiotoxicity and drug-drug interactions. Despite these mechanistic insights, limitations in pharmacokinetic data, standardized dosing, and long-term safety preclude clinical application. Future research should prioritize controlled human studies, omics-driven biomarker discovery, and evidence-based regulatory evaluation to clarify kratom's therapeutic potential and risk profile. - Source: PubMed
Publication date: 2026/04/16
Misnan EdyhamHasbullah Nur Zahidah AqilahAbd Rashid RusdiMohd Shah AishahSim Maw Shin