Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P16104 (H2AX)
 3,930 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The common age-related neurodegeneration of Parkinson's disease can result from dominant causes like increased dosage of vesicle-associated alpha-synuclein (SNCA) or recessive causes like deficiency of mitophagy factor PINK1. Interactions between these triggers and their convergence onto shared pathways are crucial, but currently conflicting evidence exists. Here, we crossed previously characterized mice with A53T-SNCA overexpression and with Pink1 deletion to generate double mutants (DMs). We studied their lifespan and behavior, histological and molecular anomalies at late and early ages. DM animals showed potentiated phenotypes in comparison with both single mutants (SMs), with reduced survival and strongly reduced spontaneous movements from the age of 3 months onwards. In contrast to SMs, a quarter of DM animals manifested progressive paralysis at ages >1 year and exhibited protein aggregates immunopositive for pSer129-SNCA, p62 and ubiquitin in spinal cord and basal brain. Brain proteome quantifications of ubiquitination sites documented altered degradation of SNCA and the DNA-damage marker H2AX at the age of 18 months. Global brain transcriptome profiles and qPCR validation experiments identified many consistent transcriptional dysregulations already at the age of 6 weeks, which were absent from SMs. The observed downregulations for Dapk1, Dcaf17, Rab42 and the novel SNCA-marker Lect1 as well as the upregulations for Dctn5, Mrpl9, Tmem181a, Xaf1 and H2afx reflect changes in ubiquitination, mitochondrial/synaptic/microtubular/cell adhesion dynamics and DNA damage. Thus, our study confirmed that SNCA-triggered neurotoxicity is exacerbated by the absence of PINK1 and identified a novel molecular signature that is detectable early in the course of this double pathology.
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PMID:Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression. 2529 18

Although the impact of MAPT (Tau) expression has been well documented for neuronal cells in the context of tauopathies and neurodegenerative diseases, the impact and role of Tau expression in cancer, and specifically cancers of neuronal origin, is in its infancy. To determine the correlation between MAPT expression and survival in pediatric neuroblastoma, MAPT gene expression for samples from the TARGET pediatric neuroblastoma dataset was assessed. Initial analyses indicated that increased MAPT expression correlated with increased overall survival in neuroblastoma but not in ovarian cancer. Expression of apoptosis- and proliferation-effector genes in the neuroblastoma samples was consistent with the MAPT related survival result. Furthermore, we determined that higher neuroblastoma expression of APP also associated with neurodegeneration, correlated with better neuroblastoma survival rates. In sum, Gene expression associated with neuronal degenerative diseases was associated with a better neuroblastoma outcome. Abbreviations: ALS: Amyotrophic Lateral Sclerosis; APP: Amyloid Precursor Protein gene; CASP3: Caspase 3 gene; CASP9: Caspase 9 gene; H2AFX: H2A histone family, member X gene; HIST1H2AL: Histone H2A type 1 gene; HIST1H2BK: Histone H2B type 1-K gene; HIST1H3J: Histone H3J gene; HIST1H4B: Histone H4B gene; HIST2H2BE: Histone H2B type 2-E gene; HUGO: human genome organization; KM: Kaplan-Meier survival curve; MAPT: Tau gene; OV: Ovarian cancer; SNCA: alpha-syneculin gene; TARDBP: Transactive response DNA binding protein 43 kDa; TCGA: the cancer genome atlas.
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PMID:MAPT (Tau) expression is a biomarker for an increased rate of survival in pediatric neuroblastoma. 3039 13