Ask about this productRelated genes to: CYP2E1 Blocking Peptide
- Gene:
- CYP2E1 NIH gene
- Name:
- cytochrome P450 family 2 subfamily E member 1
- Previous symbol:
- CYP2E
- Synonyms:
- -
- Chromosome:
- 10q26.3
- Locus Type:
- gene with protein product
- Date approved:
- 1988-03-03
- Date modifiied:
- 2015-12-09
Related products to: CYP2E1 Blocking Peptide
Related articles to: CYP2E1 Blocking Peptide
- The mouse gene Lilrb4a, an ortholog of human leukocyte immunoglobulin-like receptor B4 (LILRB4), is markedly upregulated in microglia in Alzheimer's disease models and has been implicated in Apolipoprotein E (APOE)-related signaling. However, its contribution to amyloid pathology under an APOE4 background remains unclear. Here, 5xFAD mice carrying human APOE4 were used to assess the impact of Lilrb4a reduction by genetic deletion or antisense oligonucleotide treatment. Both approaches significantly reduced cortical amyloid plaque burden and APOE4-associated cerebral amyloid angiopathy without altering amyloid-β (Aβ) production. Bulk RNA sequencing identified enrichment of peroxisome proliferator-activated receptor (PPAR)-related and broader metabolic pathways in Lilrb4a-deficient mice. Consistently, biochemical analyses showed reduced p-SHP-2, NF-κB-p65, and p-STAT1, increased p-STAT3, and induction of anti-inflammatory and clearance-associated effectors, including Arg-1, TGF-β, and Cyp2e1. In primary microglia, pharmacological interrogation supported a functional contribution of PPAR-γ signaling to the enhanced Aβ uptake and degradation associated with Lilrb4a suppression, whereas PPAR-γ agonism recapitulated key pro-clearance phenotypes in vitro and attenuated amyloid pathology in vivo. Together, these data support Lilrb4a as an APOE4-associated microglial checkpoint candidate linked to impaired amyloid clearance and identify a PPAR-linked pro-clearance program as a potential downstream component of this response. - Source: PubMed
Publication date: 2026/06/22
Nie ChangxuYang RuixiWang XiaotongJia PingZhang XueqiDai YaqiBai XueDuan SijiaLi YufengZheng PengTian XinJiang LiWang Chao - Cenobamate (CNB) demonstrates high efficacy in drug-resistant focal epilepsy, yet optimal management requires personalized strategies. This exploratory case series describes five patients selected from a cohort of 125 individuals treated with CNB, examining the relationship between pharmacogenetic (PGx) profiles and clinical outcomes. Clinical data and therapeutic drug monitoring (TDM) were integrated with targeted Next-Generation Sequencing of key metabolic genes (UGT2B7, UGT2B4, CYP2E1, CYP2B6, CYP2A6, CYP3A4, CYP2C19) to predict metabolizer phenotypes. Three patients (Cases 1, 3, 4) achieved seizure freedom or ≥50% response at sub-target or target doses (100-200 mg/day enabling early de-escalation of concomitant sodium channel blockers and valproate. This success was supported by a proactive digital communication protocol and a mandatory 100 mg clinical checkpoint. Case 2-a non-responder at 400 mg/day despite therapeutic plasma levels (28.22 mg/L)-exhibited a predicted "Ultrarapid Metabolizer" (UM) phenotype characterized by UGT2B7 Haplotype 4 and CYP2E1 duplication, suggesting possible pharmacokinetic contribution to non-response. Case 5 experienced dose-limiting toxicity at 100 mg/day; we hypothesized this toxicity could be driven by a drug-drug-gene interaction involving CNB-mediated inhibition that impairs clearance of N-desmethylclobazam (the active metabolite of clobazam) in a patient with impaired activity and intermediate function. As an exploratory case series, these findings require validation in adequately powered prospective studies. Associations between UM phenotype and non-response, and between PM phenotype and dose-limiting toxicity, represent preliminary observations that may reflect pharmacokinetic variability. Nevertheless, our experience is consistent with a personalized, sub-target dose titration strategy that may help minimize adverse events in complex polypharmacy settings. - Source: PubMed
Publication date: 2026/06/04
d'Orsi GiuseppeDi Claudio Maria TeresaCafaro AlessiaBarco SebastianoRobustella MartaLocatelli NicolòLiantonio AntonellaImbrici PaolaCiavarella GraziaRinaldi AntonioFania GiuseppeCostantino UmbertoCarella MassimoCangemi GiulianaMiscio Giuseppe - Alcoholic fatty liver disease (AFLD) is one of the most common alcohol-related liver disorders and is characterized by hepatic lipid accumulation, oxidative stress, and hepatocyte injury. Melatonin (MT), a potent antioxidant and free-radical scavenger, has been reported to exert hepatoprotective effects; however, its protective mechanisms against chronic alcohol-induced AFLD remain incompletely understood. - Source: PubMed
Publication date: 2026/06/05
Wu HaixinZhu TianqiGuo FeiZhang LuWang BingyuanLiu Guoshi - Chronic ethanol exposure activates inflammatory signaling pathways and inflicts hepatocellular damage, leading to alcohol-associated liver diseases (ALDs). ALD is one of the major causes of global burden, yet there are no FDA-approved treatment options available. This study evaluates the hepatoprotective effects of short-chain fatty acids (SCFAs), mainly sodium acetate (NaA) and sodium butyrate (NaB), against ethanol-induced inflammation and oxidative stress in both in vitro (Buffalo Rat Liver-3A [BRL3A]) and in vivo (male Wistar rats) models. The treatment of NaA and NaB and their combination was given to the cell lines where maximum viability was observed at concentrations of 1.5 mM, 5 mM, and 0.1 mM + 1 mM, respectively. Additionally, reactive oxygen species (ROS) and nuclear morphology were assessed by fluorescent staining. For in vivo samples, the hepatic injury was analyzed by serum biochemical markers. Furthermore, hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were employed, which provided structural and immunological alterations in hepatic tissue. RT-qPCR profiled the expression levels of various pro-inflammatory and anti-inflammatory cytokines, as well as cytochrome P450 E1 (CYP2E1) and antioxidative stress markers. Moreover, enzyme-linked immunosorbent assay (ELISA) quantified the essential protein targets such as TNF-α, MCP-1, IL-1β, IL-6, HO-1, and Nrf2. The administration of NaA, NaB, and their combination resulted in reduced ROS levels and expression of pro-inflammatory cytokines, preserved nuclear integrity, and neutrophil infiltration. These findings were further confirmed by in silico analysis and conserved amino acid interactions, and the affinities of NaA and NaB for TNF-α and MCP-1 were observed as compared to established inhibitors or activators. This study is the first demonstration to report the synergistic effects of NaA and NaB on the feedback loop of the nuclear factor kappa B (NF-κB) signaling pathway, suggesting their potential as promising therapeutic candidates for alleviating alcohol-induced hepatic damage. - Source: PubMed
Patel ManaliAghara HiralChadha PrashstiSolanki HarshrajsinhSharma DhrubjyotiThiruvenkatam VijayMandal Palash - Cytochrome P450 2E1 (CYP2E1) is a liver-expressed monooxygenase that metabolizes low molecular weight pollutants, drugs, and endogenous substrates such as fatty acids and ketones. Germline Cyp2e1 knockout (KO) mice were developed in the late 1990s and were initially reported to lack an overt phenotype. Subsequent studies showed that these mice are protected from liver injury caused by ethanol, high-fat diet, and chemical exposures. However, most prior work has focused on males. Here, we examined baseline effects of Cyp2e1 deletion in female and male mice. - Source: PubMed
Publication date: 2026/06/15
Stayer Kristina MKillingsworth Zaria KUnsal Kubra CalisirThornton Madison NDriggers Kylie RMendenhall Tsultrim TTomasevich Alexandra ADelaney Joe RSahin OzgurHelke Kristi LEngevik Melinda AHartman Jessica H