Project description:Hdac4 has been found to modulate symptoms in Huntington's Disease (HD) mouse models through an uknown mechanism unrelated to any enzymatic activity. We investigated the protein-protein interactions to gain insight into the role of Hdac4 in HD.
Project description:Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of the CAG nucleotide repeat in the first exon of the huntingtin (HTT) gene, with an onset between the second and third decades of life and slow progression. The pathogenesis of several of HD involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. To elucidate potential variations in gene expression in HD, a transcriptome study was conducted on 15 HD subjects and 15 controls, all of Sicilian origin, starting from peripheral blood mononuclear cell samples. A total of 7179 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with HD, i.e. all GO biological process terms encompassing ribosome functions and structure are all highly negatively expressed phenotypes, with a large number of genes being dysregulated. This leads to the hypothesis that the processing chain leading to protein translation (via ribosomes) from mRNA is somehow impaired. In addition, genes and non-coding RNAs (ncRNAs) that play a regulatory role in various transcriptional processes were dysregulated. We can hypothesize that the whole process, from transcription to translation, is somehow compromised in HD subjects who have been genetically diagnosed with the expansion of the CAG triplet of the first exon of the HTT gene.
Project description:Compared the global gene expression profiles of HD- and CON-iPSC-derived neurons We used microarrays to detail the global programme of gene expression for comparing the global gene expression profiles of HD- and CON-iPSC-derived neurons and facilitating studies of medium spiny neurons (MSN)-degenerative processes of Huntington's Disease (HD).
Project description:Huntington's disease (HD) and control GLAST-postive induced pluripotent stem cell (iPSC)-derived astrocytes underwent single-nucleus RNA-sequencing to investigate cell state diversity across control and HD patient-derived astrocytes.
Project description:We intend to screen altered genes after overexpression of miR-196a in HD transgenic mice. Two transgenic mouse lines were used in this study, including HD transgenic mice and HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. At this point, HD transgenic mice showed severve motor dysfunctions, whereas HD transgenic mice overexpressing miR-196a displayed mild motor dysfunctions.