Ask about this productRelated genes to: PSMA3 antibody
- Gene:
- PSMA3 NIH gene
- Name:
- proteasome subunit alpha 3
- Previous symbol:
- -
- Synonyms:
- HC8
- Chromosome:
- 14q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-03
- Date modifiied:
- 2016-10-05
Related products to: PSMA3 antibody
Related articles to: PSMA3 antibody
- The involvement of ubiquitin-proteasome system (UPS) impairment in Alzheimer's disease (AD) is increasing gradually yet the molecular organization of the system throughout the AD brain is poorly understood, as is the distribution of molecular markers. To systemically identify UPS-associated molecular signatures, we carried out a multi-region transcriptomic analysis of six different brain regions in AD patients and age-matched controls. The molecular perturbation of regions recapitulated the known regional vulnerability hierarchy with significant changes observed in the entorhinal cortex and hippocampus as well as middle temporal gyrus and posterior cingulate. A synchronized downregulation of UPS components was observed in the vulnerable regions indicating towards the extensive dysfunction of ubiquitin-mediated protein surveillance and proteasomal degradation. The consistent features associated with UPS disruption were linked with synaptic dysfunction, mitochondrial impairment and loss of proteostatic homeostasis as revealed by the functional analyses. We formulated a framework based on composite prioritization which combined several aspects like differential expression, network topology, regional consistency and diagnostic performance for the purpose of identifying strong biomarker candidates. The analysis revealed the most eminent global biomarkers of AD associated with UPS, namely, PSMB4, SNCA, PSMB7, PSMD1, and UBE3A. UBE2R1 (CDC34) was used to define region-specific biomarker signatures in the entorhinal cortex, UBC in the hippocampus, PSMA3 in middle temporal gyrus, PSMD4 in posterior cingulate cortex and UBE2V2 in superior frontal gyrus. These exploratory results provide the first systems-level biomarker atlas of UPS dysfunction in distinct AD brain regions and suggest that there are potential global and region-specific UPS signatures that could be used in diagnostics and drug development. - Source: PubMed
Publication date: 2026/09/29
Lakra ApurvaKumar Pravir - Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are B-cell malignancies with distinct cellular origins and microenvironmental dependencies. We aimed to identify concordant transcriptomic signatures and candidate transcriptional regulatory features between CLL CD19-positive B cells and MM-associated bone marrow-derived mesenchymal stromal cells (MSCs). Public Gene Expression Omnibus bulk RNA sequencing datasets were analyzed separately within each context using DESeq2. Differentially expressed genes (DEGs) were defined using adjusted -value < 0.05 and absolute log fold change > 1. Cross-disease analyses assessed overlap, directionality, log fold-change concordance, expressed-gene background-adjusted enrichment, coexpression structure, and transcription factor annotation. We found a focused concordant gene-level signature shared across contexts. We identified 5965 DEGs in CLL and 1021 DEGs in MM; 323 were shared, and 262 were concordantly regulated, including 52 upregulated and 210 downregulated genes in both contexts. These genes showed strong log fold change concordance between CLL and MM. No Gene Ontology or Kyoto Encyclopedia of Genes and Genomes terms remained significant after expressed-gene background correction, supporting stronger gene-level than pathway-level evidence. Exploratory coexpression analysis identified PSMA3-AS1, SNORD58A, 100124516, MSS51, and 652966 as the top degree-ranked hubs and seven shared differentially expressed transcription factor candidates: MAFB, MYB, CCDC17, MYSM1, ZMAT1, ZNF491, and ZNF789. Expression-matched permutation analysis did not support global transcription factor enrichment. These findings support a cross-contextual concordant transcriptomic signature shared by CLL CD19-positive B cells and MM-associated MSCs, warranting validation in harmonized cohorts and experiments. - Source: PubMed
Publication date: 2026/08/13
Tondar AbtinMarín David HervásLiñán Laura CalvetBepari Asim Kumar - Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss driven by mitochondrial dysfunction, oxidative stress, and proteostasis collapse, for which current therapies remain symptomatic. This study investigated the neuroprotective effects of Eucalyptus citriodora essential oil (ECEO) on 6-hydroxydopamine (6-OHDA)-induced toxicity in N2a neuroblastoma cells. GC-MS analysis showed that ECEO was dominated by oxygenated monoterpenes, mainly citronellal (60.7%), isopulegol (16%), and citronellol (5.7%). In silico analysis of these constituents showed favorable ADMET profiles, predicted blood-brain barrier permeability, and non-overlapping multitarget engagement across enzymes, GPCRs and nuclear receptors. At the cellular level, ECEO pretreatment significantly restored cell viability (86.7% of control), reduced LDH release, attenuated ROS and NO, and limited mitochondrial depolarization. Quantitative 2D-gel/MALDI-TOF/TOF proteomics identified 94 differentially abundant proteins, of which 20 showed validated PD-related associations (KEGG, Gene4PD, and DisGeNET databases). ECEO pretreatment modulated 12 of these proteins across mechanistically coherent pathways: (i) reversal of 6-OHDA-induced reprogramming of energy metabolism, by normalizing the glycolytic enzymes PKM and PGK1 and restoring the TCA enzyme SUCLG2; (ii) reinforcement of proteostasis through PSMB4 and PSMA3 induction, VCP upregulation and attenuation of ER stress marker HSPA5/BiP; (iii) preservation of mitochondrial and cytoskeletal integrity through PHB1 induction and bilateral TUBB5 restoration. Overall, our results suggest that ECEO exerts significant neuroprotective effects in a cellular PD model by coordinately modulating energy metabolism, proteostasis, antioxidant defense, and structural integrity. Given its predominance in oxygenated monoterpenes the neuroprotective activity of ECEO may result from the combined contribution of the major constituents supporting further investigation in age-related neurodegeneration. - Source: PubMed
Publication date: 2026/08/17
Abidi AmelShaba EnxhiVantaggiato LorenzaKouki OumaymaMasmoudi-Kouki OlfaBini LucaUlivieri CristinaLandi ClaudiaGhrairi Taoufik - Ubiquitin-independent degradation (UID) by the 20S proteasome represents a key pathway for mainly regulating intrinsically disordered proteins (IDPs), yet the degron motifs that govern this process remain poorly defined. In this chapter, we describe experimental strategies to identify UID degrons that mediate degradation by the catalytic 20S proteasome particle. Combining high-throughput 20S substrate assays in vitro with analyses of PSMA3 C-terminal binding proteins, we identified numerous IDPs, including p21, as potential substrates. Using bimolecular fluorescence complementation (BiFC) and split-luciferase reporter assays, we mapped the degron within p21. Systematic mutagenesis and peptide- and fragment-based assays delineated the minimal degron sequence, while CRISPR-Cas9-mediated editing of the endogenous protein confirmed its physiological role in proteasomal turnover. This integrated workflow-spanning degron mapping to functional validation-provides a generalizable framework for uncovering ubiquitin-independent degrons. - Source: PubMed
Shaul Yosef - Heart failure with preserved ejection fraction (HFpEF) is an increasingly common form of heart failure (HF) that is best understood as a systemic, multiorgan syndrome rather than a disease of left-ventricular filling alone. This review has three specific aims: first, to synthesize genetic and molecular pathways that are most relevant to non-ischemic HFpEF; second, to distinguish HFpEF-enriched mechanisms from evidence extrapolated from ischemic cardiomyopathy or HFrEF; and third, to consider translational implications for populations with high consanguinity, including the Kingdom of Saudi Arabia. The available evidence indicates that chronic inflammatory signaling involving CCL2, CCL5, TLR3, PTGS2/COX-2, IL-6/JAK/STAT3, NF-kB, and NLRP3 acts upstream of endothelial dysfunction, nitric-oxide/cGMP/PKG impairment, mitochondrial reactive oxygen species generation, and fibroblast activation. Extracellular-matrix regulators including ASPN, COL1A1, and MMP2 then amplify collagen deposition and myocardial stiffness, whereas mitochondrial genes and proteins such as ATP5C1 contribute to impaired oxidative phosphorylation, reduced ATP reserve, defective fatty-acid oxidation, and blunted mitophagy. Protein-quality-control pathways involving HSP90AA1, CCT2/CCT5, PSMA3, and stress-responsive STAT3 further link metabolic stress to proteotoxic injury. Epigenetic mechanisms, including DNA methylation and microRNAs such as miR-155, miR-1297, and miR-4649-3p, add a regulatory layer that may improve risk stratification but remains insufficiently validated for routine clinical use. In high-consanguinity settings, recessive cardiomyopathy variants can cluster in families and contribute to earlier NIHF presentations; however, population-level HFpEF-specific variant frequencies remain limited, and findings from HFrEF or dilated cardiomyopathy should be interpreted as candidate pathway evidence rather than definitive HFpEF markers. Translationally, SGLT2 inhibitors, mineralocorticoid-receptor antagonism, biomarker panels, and structured genetic evaluation provide the most clinically actionable bridge from molecular mechanisms to precision HFpEF care. - Source: PubMed
Publication date: 2026/07/11
Abou Al-Saud Sara