Ask about this productRelated genes to: PARK7 antibody
- Gene:
- PARK7 NIH gene
- Name:
- Parkinsonism associated deglycase
- Previous symbol:
- -
- Synonyms:
- DJ-1, DJ1, GATD2
- Chromosome:
- 1p36.23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-08-07
- Date modifiied:
- 2018-07-11
Related products to: PARK7 antibody
Related articles to: PARK7 antibody
- Anastrozole (ANZ) is a commonly used aromatase inhibitor in the treatment of hormone-dependent breast cancer. Despite its toxicity profile reported in different studies, the neurotoxic effects against this drug have not been explored yet. The present study was aimed at investigating the neurotoxic effects of ANZ in Sprague Dawley rats using comprehensive biochemical, molecular and histopathological analysis. Rats were divided into control and ANZ treated (0.1, 0.2 and 0.5 mg/ kg) doses. It was found that ANZ intoxication promoted the gene expression of NLRP3, PYCARD, CASP1, IL1-β, IL18, TXNIP, SNCA, and LRRK2 while suppressing the expression of PARK2, PINK1, PARK7 and UCHL1 in dose dependent manner. Moreover, ANZ exposure significantly reduced the antioxidant defense systems as shown by reduction in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione-peroxidase (GPx) and heme oxygenase-1 (HO-1) coupled with elevated levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Similarly, ANZ administration showed marked reductions in the levels of BDNF, NGF, GDNF PSD-95, and synaptophysin while increasing the levels of NF-κB, COX-2, TNF-α, IL-1β, and IL-6. Nonetheless, ANZ exposure provoked the levels of Caspase-9, Bax, and Caspase-3 while inhibiting the levels of Bcl-2. Histological examination confirmed the dose-dependent neuronal degeneration such as vacuolization, pyknosis and structural disorganization. Collectively, these results showed that ANZ causes significant neurotoxicity due to oxidative stress, inflammation, and apoptosis resulting in neuronal survival and function dysfunction. This study shows the importance of careful therapeutic use of ANZ and laid down the foundation for further research on the neurological safety profile of ANZ. - Source: PubMed
Publication date: 2026/05/15
Alghamdi AmaniJamil SalimAlkhoshaiban Abdulaziz SalehAzmat Muhammad BilalAlzahrani Fuad MAlzahrani Khalid JAlsharif Khalaf FHassan Hesham M - Chaperone-mediated autophagy (CMA) promotes cancer cell survival by selectively removing oxidatively damaged proteins, yet its precise molecular mechanisms and role in redox adaptation remain incompletely understood. This study aimed to elucidate the function of CMA in regulating oxidative stress resistance in gastric cancer (GC) cells, focusing on the LAMP2A-DJ-1 regulatory axis. LAMP2A expression was assessed in GC tissues and cell lines via immunohistochemistry, qPCR, and western blot. Oxidative stress models were established using hydrogen peroxide (H₂O₂). Genetic manipulation of LAMP2A was performed to evaluate its impact on cell proliferation, apoptosis, and CMA substrate recognition. Protein interactions were examined by co-immunoprecipitation and immunofluorescence. We found that LAMP2A was upregulated in GC and further induced by oxidative stress. Knockdown of LAMP2A impaired CMA activity, sensitizing GC cells to H₂O₂-induced apoptosis. DJ-1, an antioxidant protein, was identified as a CMA substrate containing a conserved KFERQ-like motif. Oxidative stress enhanced DJ-1-LAMP2A interaction and promoted their lysosomal colocalization. LAMP2A deficiency led to accumulation of hyperoxidized DJ-1, concomitant with upregulation of pro-apoptotic BAX and downregulation of anti-apoptotic Bcl-2. We identify hyperoxidized DJ-1 as a novel CMA substrate and demonstrate that LAMP2A-dependent clearance of oxidized DJ-1 constitutes a key adaptive mechanism that maintains redox homeostasis and promotes survival in gastric cancer cells under oxidative stress. - Source: PubMed
Publication date: 2026/05/15
Le ShuangshuangGuo TongtongYang MengTang TianjuanLiu ZhijieZheng YangPang Maogui - Parkinson's disease (PD) is clinically heterogeneous, yet the genetic architecture underlying this heterogeneity remains incompletely understood. We examined the genetic correlates of four complementary PD subtyping frameworks: the clinical motor subtype (tremor-dominant [TD] vs. postural instability/gait difficulty [PIGD]), alpha-synuclein seed amplification assay status (SAA+ vs. SAA-), the pathological subtype (brain-first vs. body-first, based on the presence of REM sleep behavior disorder), and the data-driven subtype (diffuse malignant [DM] vs. mild-motor predominant [MMP] vs. intermediate [IM]). We analyzed 1390 PD patients from the Parkinson's Progression Markers Initiative (PPMI) with genotypes available for seven PD-associated genes (, , , , , , ), including specific variant resolutions (, ; , severe variants; ), and (ε2/ε3/ε4 alleles). Genetic variant frequencies were compared across subtypes using chi-square or Fisher's exact tests with the Benjamini-Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cramér's V. multivariable logistic regression estimated adjusted odds ratios with Wald-based 95% confidence intervals. Among genotyped PD patients, carriers constituted 13.7% (190/1390; 170 , 18 ), 8.6% (119/1390; 96 , 23 severe), and 2.0% (28/1390; all ). ε4 carriers comprised 23.4% (323/1380). SAA-negative patients were markedly enriched for variants (37.1% vs. 10.2%, = 3.7 × 10, q < 0.001, V = 0.25), specifically (28.5% vs. 9.6%, = 4.9 × 10, q < 0.001) and (7.9% vs. 0.5%, = 2.7 × 10, q < 0.001). Body-first PD was enriched for carriers (12.3% vs. 6.7%, = 0.004, q = 0.021) and had less carriers (7.9% vs. 15.0%, = 0.002, q = 0.013). The DM subtype had the highest frequency (14.0% vs. MMP 5.9%, < 0.001, q = 0.003). After FDR correction, 10 out of 48 univariate tests remained significant. Clinical subtypes (TD vs. PIGD) showed only nominal differences that did not survive FDR correction. The genotype did not differ across any framework. PD subtypes defined by alpha-synuclein pathology (SAA), pathological onset pattern (brain-first/body-first), and data-driven classification (DM/MMP/IM) show distinct genetic profiles that survive multiple comparison correction. variants strongly associate with SAA negativity (V = 0.25); variants associate with the severe body-first onset and the diffuse malignant subtype. - Source: PubMed
Publication date: 2026/04/13
Negida AhmedAbouelmagd Moaz ElsayedHamed Belal MohamedHawas YousefDziri AyaNegida YasminBerman Brian DBarrett Matthew J - Diabetic nephropathy (DN) is a major diabetic complication, and while DJ-1 has been shown to mitigate renal ischemia/reperfusion injury, its role in high glucose-induced podocyte damage remains unclear. This study aimed to investigate the function and mechanism of DJ-1 in high glucose-induced injury of human podocyte cells (HPCs). Using RNA-seq analysis, we identified that high glucose broadly affected multiple signaling pathways related to cell growth, death, and signal transduction. Notably, DJ-1 expression was downregulated under high glucose conditions. Overexpression of DJ-1 significantly attenuated high glucose-induced HPC apoptosis. Mechanistically, DJ-1 promoted the phosphorylation of ERK1/2 and facilitated the nuclear translocation of p-ERK1/2. This activated the ERK1/2 pathway and upregulated the expression of NF-κB p65 and AP-1, thereby suppressing HPC apoptosis under high glucose conditions. In summary, our findings reveal that DJ-1 protects against high glucose-induced HPC injury by activating the ERK1/2 pathway and enhancing NF-κB p65 and AP-1 expression, providing new insights into the molecular mechanisms of DJ-1 in diabetic nephropathy. - Source: PubMed
Publication date: 2026/04/17
Tian XiaochenLi JingHan TaoZhang LeishengLu PingLiu Yusheng - Regional brain atrophy has been observed in dementia with Lewy bodies (DLB), yet determinants of regional vulnerability remain unclear. Using imaging transcriptomics, we examined whether normative gene expression patterns relate to regional atrophy in DLB. We included 164 DLB patients (49 women) and 164 age- and sex-matched healthy controls from three European centres and the Mayo Clinic, USA. Volumetric atrophy was quantified from T1-weighted MRI across 58 left-hemispheric regions using w-scores. Normative expression of twelve genes implicated in alpha-synuclein, beta-amyloid, and tau pathology was extracted from the Allen Human Brain Atlas. DLB patients showed diffuse atrophy across most regions. In the full cohort, normative expression of MAPT, PINK1, and PSEN2 predicted regional atrophy after correction for spatial autocorrelation, although none survived multiple-testing correction. In the Mayo Clinic sub-cohort, expression of APP, BIN1, GBA, MAPT, PINK1, SNCA, and TMEM175 significantly predicted atrophy and survived multiple-testing correction. Random forest models did not outperform spatial null models in the full cohort, but PARK7, PINK1, and PSEN2 consistently emerged as important predictors. A significant global model was observed in the Mayo Clinic sub-cohort, driven by GBA, LRP1, and PINK1. These findings suggest that normative gene expression partially contributes to regional brain atrophy in DLB. - Source: PubMed
Publication date: 2026/04/16
Habich AnnegretBaumann Janna MSchwarz Christopher GPrzybelski Scott AInguanzo AnnaOppedal KetilBlanc FrédéricLemstra Afina WHort JakubBoeve Bradley FAarsland DagWestman EricDierks ThomasKantarci KejalJonkman Laura EFerreira Daniel