Ask about this productRelated genes to: ATXN2 Blocking Peptide
- Gene:
- ATXN2 NIH gene
- Name:
- ataxin 2
- Previous symbol:
- SCA2, TNRC13
- Synonyms:
- ATX2
- Chromosome:
- 12q24.12
- Locus Type:
- gene with protein product
- Date approved:
- 1991-08-06
- Date modifiied:
- 2019-04-23
Related products to: ATXN2 Blocking Peptide
Related articles to: ATXN2 Blocking Peptide
- Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal, early-onset neurodegenerative diseases. The most common genetic cause of FTD and ALS is a G4C2 hexanucleotide repeat expansion in the C9orf72 gene. This mutation leads to the production of toxic dipeptide repeat proteins (DPRs), via repeat-associated non-AUG (RAN) translation. These DPRs disrupt stress granule (SG) dynamics, with SG regulators such as Ataxin-2 (ATXN2) implicated in disease risk. The integrated stress response (ISR), a key driver of SG formation via eIF2α phosphorylation, has been linked to C9orf72 expansions, but the role of individual DPRs in ISR activation remains unclear. Here, using Drosophila models expressing physiologically relevant repeat length DPRs, we identify poly(GR) as a novel activator of the ISR, inducing early and sustained eIF2α phosphorylation and SG accumulation prior to motor decline. Genetic inhibition of the ISR or knockdown of ATX2, the Drosophila orthologue of ATXN2, rescues motor deficits in these models. ATXN2 knockdown also reduces poly(GR) toxicity in mouse primary neurons. These findings position poly(GR) as a key driver of ISR activation and highlight ATXN2 and the ISR as promising therapeutic targets in C9orf72-associated FTD/ALS. - Source: PubMed
Publication date: 2026/05/05
Harper Nikki SSharpe Joanne LSperanza JasmineGulia RavinderChen Jeffrey XAllen Scott PAtwal Manpreet SPickering-Brown StuartLivesey Matthew RBennett Craig LProkop AndreasLa Spada Albert RWest Ryan J H - Lauerer et al. (Acta Neuropathol Commun 13:157, 2025) recently investigated the role of ATXN2 variants, including intermediate CAG repeats and a 9-bp duplication, in spinocerebellar ataxia type 3 (SCA3). While their study contributes valuable data, several of their interpretations diverge from our previous findings and require clarification. Our original hypothesis was not that the duplication alone modified age at onset, but that its effect emerges in combination with an intermediate-length ATXN2 allele (29 CAGs). Their claim of a protective effect is unsupported by non-significant results, which cannot establish equivalence. Furthermore, evidence from multiple studies demonstrates that both ATG1 and ATG2 can initiate translation, with redundancy explaining the in vivo ~ 140-145 kDa ATXN2 protein, thereby countering the assertion that the duplication is relevant only at the DNA level. We also correct the misattribution of our segregation analyses and emphasize that low frequency does not negate biological significance, as rare variants can act as genetic modifiers. Taken together, convergent DNA, RNA, and protein evidence supports the relevance of the ATXN2 9-bp duplication as part of the broader network of modifiers in SCA3. - Source: PubMed
Publication date: 2026/05/01
Laffita-Mesa Jose MiguelPaucar MartinSvenningsson Per - Non-small cell lung cancer (NSCLC) contains rare cancer stem cells (CSCs) that contribute to relapse and drug resistance. Bulk RNA-seq overlooks these cells due to its averaging of expression across all cell types, whereas standard single-cell RNA-seq (scRNA-seq) analyses often struggle to reliably identify these rare CSC states. To address this, we developed an scRNA-seq pipeline that integrates machine learning with explainable AI (XAI) to detect CSC-like epithelial cells in NSCLC (GSE198099, n = 2 patients; analyses supported by effect size-based validation despite limited statistical power). Patient-derived scRNA-seq profiles underwent quality control and batch correction using scVI, and annotated using CellTypist. A 45-gene stemness score was used to identify candidate CSC-like states. Four machine learning models (Logistic Regression, LightGBM, XGBoost, and CatBoost) were trained to refine the CSC-like state identification. SHAP-based feature attribution analyses converged on six key biomarkers: DLL1, ITGA6, ATXN2, NOTCH1, DCLK1, and PUM1. These biomarkers are involved in regulating transcription, adhesion, cytoskeletal dynamics, and post-transcriptional control. Pathway analysis and validation using TCGA validation data provided supportive evidence for the biological relevance of these biomarkers. This framework provides a methodologically reproducible approach to reveal rare CSC-like states with improved mechanistic clarity, providing candidate biomarkers for studying NSCLC tumor plasticity. - Source: PubMed
Publication date: 2026/04/22
Munisankar SharathKumar RThiyagaraj Anand - Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis type 13 (ALS13) are triggered by polyglutamine expansion in Ataxin-2 (ATXN2). To understand these neurodegenerative disorders at the molecular level, the brains of 10-month-old -CAG100-knockin mice were analyzed as microglial, astroglial and neuronal fractions via global RNA sequencing. Data were validated by comparison with the spinal cord oligonucleotide microarray profile or filtered by RNA-seq consistency. Here, we show that the mutation causes a massive inflammatory response in microglia and a reciprocal loss of neuronal transcripts in glial fractions, suggesting severe synapse loss. Beyond these general neurodegenerative signs, we identify pathognomonic changes in the machinery for protein translation and RNA splicing. Glial fractions showed upregulation of (to 2082%), , , , , , , , and as an unspecific neuroinflammatory signature, versus downregulation of axonal (to <19%), and synaptic , , , and mRNAs correlating with circuit disconnection. In all fractions, reductions in , , and were noted versus disease-specific inductions of ribosomal subunits, presumably mirroring the partial loss-of-function of ATXN2 as RNA translation modulator. Selective accumulations of embryonic factors and versus downregulation of adult specify the mutation impact on splicing and translation elongation. As a potential underpinning of toxic gain-of-function, the proteostasis transcript appeared increased in astroglial and microglial fractions. These transcriptome data suggest altered ribosomal and spliceosome machinery, with massive microgliosis versus mild astrogliosis, at the core of SCA2 and ALS13. - Source: PubMed
Publication date: 2026/04/15
Auburger GeorgKandi Arvind ReddyVutukuri RajkumarAlmaguer-Mederos Luis-EnriqueGispert SuzanaSen Nesli-EceKey Jana - Spinocerebellar Ataxia type 2 (SCA2), caused by CAG repeat expansions in ATXN2, involves a multifaceted molecular pathophysiology. Although immune system involvement is an emerging area of focus in SCA2 research, the profile of peripheral lymphocyte subsets remains largely unexplored. - Source: PubMed
Publication date: 2026/04/19
Vázquez-Mojena YaimeéRodríguez-Labrada RobertoMartínez Martí LisisHorruitiner Gutiérrez IreniaCórdova-Rodríguez YanetsyZamora-Fung RolandoFernández-Herrera Mario EOrtega Sanchez RicardoZamora-Loyarte Diana IrisLeyva Medrano LilianFeria Rodríguez MabelRobinson-Agramonte María de Los AngelesPavón-Fuentes NancyVelázquez-Pérez Luis