ATXN3 (Ataxin 3)

In addition, we observed aberrant RNA splicing changes in KI mice, particularly in oligodendrocyte signature genes. Collectively, these novel findings position the spinal cord as a primary and early site of SCA3 pathogenesis and underscore its potential both as a sensitive regional biomarker for disease progression and as a key target for therapeutic intervention.

In addition, it has been established that a growing list of acquired causes may also mimic HD, including autoimmune illnesses such as primary antiphospholipid syndrome, paraneoplastic chorea, and anti-IGLON5. Here we aim to review the epidemiology, aetiology, clinical and laboratory findings of the wide range of conditions associated with HD phenocopies, and proceed to suggest a practical diagnostic approach to the investigation of HD phenocopies taking into account the age at onset, ethnicity, and geographic location of individuals.

ATXN3 overexpression stabilized P53 in C33A/HeLa and increased p-STAT5 in SiHa, with inverse effects upon silencing. The findings suggest that hypoxia promotes the progression of subtypes of cervical cancer by regulating ATXN3-enhanced P53/p-STAT5 levels, which may provide a novel therapeutic strategy for clinical applications.

Aoki et al. demonstrated that Praja1 ubiquitinates and degrades tau, a key molecule in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal syndrome, furthering our understanding of the role of Praja1 in neurodegenerative diseases and potential therapeutic approaches.

We identified novel MAML2 fusion partners, most of which likely represent passenger alterations, possibly arising from genomic instability or impaired p53 function. However, ATXN3::MAML2 fusions, previously reported in a pre-cancerous pancreatic disease case, may represent a pathogenic alteration warranting further investigation.

It further evaluates its potential as a therapeutic target and biomarker, emphasizing recent findings that position ATXN3 as a modulator of immune checkpoints and tumor microenvironmental remodeling. By consolidating diverse studies, we aim to provide a timely and focused platform for researchers exploring ATXN3-based strategies in precision oncology.

P1/2, N=68, Recruiting, Vico Therapeutics B. V. | Trial completion date: Sep 2025 --> Oct 2028 | Trial primary completion date: Sep 2025 --> Apr 2028

Furthermore, ATXN3 exhibits a positive correlation with ZEB1 expression levels and serves as a predictor of poor prognosis in human GBM specimens. Collectively, our study elucidates a critical ATXN3-ZEB1 signaling axis in EMT and invasion, thereby providing a rationale for potential therapeutic interventions against GBM.

Pronounced reductions in myelin-enriched lipids suggest that lipid dysregulation could underlie white matter atrophy in SCA3. This study establishes the basis for future work elucidating the mechanistic, biomarker, and therapeutic potential of lipids in SCA3.

Furthermore, we demonstrated that ATXN3 promoted the occurrence and development of HCC by regulating TAZ. Therefore, our study revealed the oncogenic function of ATXN3 and an interesting deubiquitination mechanism of ATXN3 and TAZ in HCC, providing new insights into the diagnosis and treatment of HCC.

In conclusion, AST administration increased antioxidant capacity, reduced both cellular and mitochondrial oxidative stress, and improved mitochondrial quality control processes through fusion, fission, and autophagy. These mechanisms collectively reduced intracellular mutant ataxin-3 protein aggregation, thereby achieving therapeutic efficacy in the SCA3 model.

Overall, a HF diet combined with chemotherapy is associated with neuroinflammatory and neurodegenerative gene expression changes in this mouse model; dietary enrichment of EPA and DHA attenuated these effects. Further studies are needed to understand how diet impacts behavioral outcomes of CRCI.