DARPP-32 (Phospho-Thr34) Polyclonal Antibody
- Known as:
- DARPP-32 (Phospho-Thr34) Polyclonal Antibody
- Catalog number:
- 12369
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Signalway
- Gene target:
- DARPP-32 (Phospho-Thr34) Polyclonal Antibody
Related products to: DARPP-32 (Phospho-Thr34) Polyclonal Antibody
Related articles to: DARPP-32 (Phospho-Thr34) Polyclonal Antibody
- has been implicated in tumor progression in several malignancies; however, population-level genetic evidence supporting its role in intrahepatic cholangiocarcinoma (ICC) remains limited. This study aimed to investigate the association between and ICC risk and prognosis using genetic and multi-omics analyses. Multiple public datasets were integrated, including finn-b-C3_LIVER_INTRAHEPATIC_BILE_DUCTS, ebi-a-GCST90018583, eqtl-a-ENSG00000131771, GSE138709, The Cancer Genome Atlas (TCGA)-ICC, and FU-iCCA. Two-sample Mendelian randomization (MR) was performed to evaluate the genetic association between expression and ICC risk. expression patterns were further characterized using single-cell and bulk transcriptomic analyses. Expression validation was conducted using TCGA-ICC data and tissue microarray immunohistochemistry. Survival analyses were performed using the FU-iCCA cohort and institutional clinical samples. MR analysis identified as significantly associated with increased ICC risk ( < 0.05, OR > 1), and sensitivity analyses supported the robustness of the results. Single-cell analysis demonstrated enrichment of PPP1R1B expression in malignant cell populations. Bulk transcriptomic datasets and immunohistochemical validation confirmed elevated PPP1R1B expression in tumor tissues. High PPP1R1B expression was significantly associated with poorer overall survival. Genetic and multi-omics evidence supports PPP1R1B as a risk-associated and potential prognostic biomarker in ICC, providing a translational genomics framework for future biomarker development. These findings complement previously reported functional studies and strengthen the biological relevance of in ICC. - Source: PubMed
Publication date: 2026/07/25
Chen ZhuomiaoyuCao FumeiLi Zhao - The growing number of omics datasets in public repositories provides an opportunity to enhance data reusability through data integration; however, complex statistical barriers often hinder the effective combination of independent studies. To address this problem, we present MetaOmixTools, an interactive web-based suite that streamlines the meta-analysis of ranked feature lists and functional enrichment profiles. The platform integrates 2 primary modules-MetaRank and MetaEnrich-within a code-free environment. MetaRank generates robust consensus rankings from multiple lists by implementing weighted (e.g., rank product) and unweighted (e.g., robust rank aggregation) strategies, while MetaEnrich performs functional meta-analyses by combining probability values from individual overrepresentation analyses using established statistical techniques. Using case studies, we established consensus rankings for acute spinal cord injury across heterogeneous platforms, identifying conserved inflammatory marker genes in the up-regulated gene list (e.g., , , and ) and synaptic loss genes in the down-regulated gene list (e.g., , , and ), and also characterized inverse functional intersections between melanoma brain metastasis and neurodegenerative diseases. By providing intuitive, real-time visualization and reproducible workflows, MetaOmixTools empowers the research community to extract consistent biological insights from multistudy data. We have made MetaOmixTools freely available at https://bioinfo.cipf.es/metaomixtools/. - Source: PubMed
Publication date: 2026/06/30
Grillo-Risco RubénTiurin Maksym KupchykPerpiñá-Clérigues CarlaCordero Felipe Francisco JJuárez Samuel LozanoIglesia-Vayá MaríaGarcía-García Francisco - Huntington disease (HD) is a progressive neurodegenerative disease caused by an expanded CAG repeat in the () gene, leading to the accumulation of mutant HTT (mHTT). IL17A (interleukin 17A), a proinflammatory cytokine primarily secreted by Th17 and γδ T cells, has been implicated in immune-mediated neurodegeneration. However, the role of IL17A in the pathogenesis of HD remains poorly understood. Here, we identify IL17A as a critical pathogenic factor in HD that promotes neuroinflammation, mHTT aggregation, and autophagy-lysosomal dysfunction. IL17A disrupts autophagic flux by downregulating CTSB and CTSD, inducing SQSTM1/p62 and MAP1LC3B-II/LC3-II accumulation, and impairing lysosomal reformation. Mechanistically, IL17A suppresses lysosomal biogenesis by inhibiting the nuclear translocation of TFE3. This regulation occurs via a novel GSK3B/GSK-3β-TFE3 signaling pathway. Therapeutic neutralization of IL17A with a monoclonal antibody (IL17A mAb) ameliorates disease phenotypes in R6/2 HD mice, improving motor performance, extending survival, and reducing gliosis. IL17A mAb also attenuates mHTT aggregation and enhances neuroprotective signaling, as evidenced by increased expression of DLG4/PSD-95, phosphorylated CREB1, and BDNF. Moreover, IL17A mAb restores autophagy-lysosomal function by facilitating the clearance of protein aggregates and upregulating lysosomal enzymes and biogenesis markers, including CTSB, CTSD, PIP5K1A, and LAMP2. These findings establish IL17A as a key modulator of HD pathophysiology and highlight IL17A inhibition as a promising therapeutic strategy for targeting autophagy-lysosomal dysfunction in HD. 3-MA; 3-methyladenine; Aβ, amyloid beta; AIF1/Iba1, allograft inflammatory factor 1; ALP, autophagy-lysosomal pathway; ALR, autophagic lysosomal reformation; ATG7, autophagy related 7; ATG5, autophagy related 5; Baf A1, bafilomycin A1; BBB, blood-brain barrier; BDNF, brain derived neurotrophic factor; CSF, cerebrospinal fluid; CTSB, cathepsin B; CTSD, cathepsin D; DLG4/PSD-95, discs large MAGUK scaffold protein 4; GFAP, glial fibrillary acidic protein; GSK3B/GSK-3β, glycogen synthase kinase 3 beta; HD, Huntington disease; HTT, huntingtin; ICV, intracerebroventricular; IL17A, interleukin 17A; IL17A mAb, IL17A monoclonal antibody; IL17RA, interleukin 17 receptor A; IV, intravenous; LAMP2, lysosomal-associated membrane protein 2; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 beta; mHTT, mutant HTT; RBFOX3/NeuN, RNS binding protein, fox-1 homolog (C. elegans) 3; p-CREB1/CREB, phospho-cAMP responsive element binding protein 1; PIP5K1A, phosphatidylinositol-4-phosphate 5-kinase, type 1 alpha; PPP1R1B/DARPP-32, protein phosphatase 1 regulatory inhibitor subunit 1B; rIL17A, recombinant IL17A; SQS, self-quenched substrate; SQSTM1/p62, sequestosome 1; MAPT/tau, microtubule-associated protein tau; TDG, tideglusib; TFE3, transcript factor E3; TFEB, transcript factor EB; Th17, T helper 17; TX-100, Triton X-100; WT, wild-type. - Source: PubMed
Publication date: 2026/08/18
Chen Kai-PoJu Tz-Chuen - Schizophrenia is a complex neuropsychiatric disorder associated with genetic variants of the dystrobrevin-binding protein 1 (Dtnbp1) gene. While cognitive deficits in male Dtnbp1 mutant mice are well-documented, the impact of this mutation on female subjects remains underexplored. This study investigated the behavioral and molecular effects of Dtnbp1 deficiency in male and female knockout (Dys) mice, highlighting sex-specific cognitive, social, and molecular signaling impairments relevant to schizophrenia. Female Dys-/- mice exhibited an anxiolytic phenotype with intact threat memory and normal novel object recognition memory. However, they displayed profound deficits in temporal order recognition memory and multiple domains of social behavior. Conversely, male Dys mice largely maintained normal social recognition. Molecular analyses revealed dysregulation of the dopaminergic system specifically in the prefrontal cortex (PFC) of female Dys mice. This dysfunction was characterized by reduced mRNA expression of the dopamine receptors D1 (Drd1) and D2 (Drd2), as well as aberrant activity of canonical (DARPP-32) and noncanonical (GSK3β) signaling pathways. Collectively, these findings demonstrate that dysbindin-1 deficiency drives distinct, female-specific vulnerabilities in behavioral and molecular alterations relevant to neuropsychiatric conditions, providing insight into the sex-dependent pathophysiology of social and cognitive deficits in preclinical models of schizophrenia. - Source: PubMed
Publication date: 2026/07/19
Chang Hsin-AnPan Wei-TingWu I-LinLin Yen-YueChou Li-HanLiao Sylvia Yu-YaLu Jyun-YanHe Zi-TongHuang Cathy Chia-Yu - Amid a global shift toward older populations, understanding the mechanisms of cognitive aging is a public health priority. Processing speed shows age-related decline and predicts dementia risk. Neuroimaging links dopaminergic system integrity to cognitive performance in aging, but the contribution of common genetic variation remains unclear. This study tested whether common dopaminergic variants influence 12-year processing speed decline, performance at age 70, and other cognitive domains, with exploratory analyses of post-mortem pathology. A total of 89 linkage disequilibrium-independent variants (derived from 957 SNPs) across nine dopamine pathway genes (TH, DDC, DRD1-3, SLC6A3, COMT, DBH, PPP1R1B) were analysed in 1,539 participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age. Across single-variant, gene-based, and unweighted pathway allele score analyses, no associations survived multiple testing correction (Bonferroni p < 5.62 × 10⁻4). For processing speed decline, the strongest nominal signals were DRD2 rs10789943 (p = 0.0066) and DBH rs2005663 (p = 0.0074), followed by DRD2 rs12805897 (p = 0.013). For performance at age 70, the leading signal was DRD2 rs11214607 (p = 0.0025). Gene-based tests were non-significant (strongest: DRD2 for slopes p = 0.063; DRD2 for intercepts p = 0.019), and the dopamine pathway allele score was unassociated with decline (β = 0.001, p = 0.969) and performance (β = 0.009, p = 0.721). Null findings extended to fluid reasoning, episodic memory, and vocabulary, and to post-mortem analyses (neuropathology n = 116; synaptic density n = 50), including SNP-marker and marker-trajectory tests. With 80% power to detect single variants explaining at least 1.19% of variance and allele score effects explaining at least 0.51% of variance, no moderate-to-large effects of common dopaminergic variation on cognitive aging trajectories were detected. Smaller effects, or mechanisms not captured by common variant analyses such as rare variants, epigenetic regulation, or gene-environment interactions, may contribute to individual differences in cognitive aging. - Source: PubMed
Publication date: 2026/07/17
Rose Monica AnonaRobinson Andrew CPayton Antony