Sporadic ALS Australia
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ABSTRACT:
PROVIDER: PRJNA933342 | ENA |
REPOSITORIES: ENA
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Project description:Differentiated motor neurons from hiPSC derived from peripheral nerve fibroblasts of sporadic ALS patients and evaluated the gene expression profile by means microarray-linked to specific analysis tools. Two-condition experiment, ALS patients motor neurons vs. controls. Biological replicates: 3 ALS replicates, 3 control replicates.
2015-04-25 | E-GEOD-68240 | biostudies-arrayexpress
Project description:Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control
2015-07-19 | E-GEOD-67196 | biostudies-arrayexpress
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls.
2007-09-26 | E-GEOD-833 | biostudies-arrayexpress
Project description:We aimed to identify muscle-specific common miRNA profile associated with the etiopathogenesis of sporadic ALS (sALS). For this purpose, we isolated total RNA from the skeletal muscle tissues of 10 sALS patients and 5 control individuals, and miRNA expression of sALS patients and controls were analyzed using Affymetrix GeneChip miRNA 4.0 Array. In order to find out differentially expressed miRNAs, we used The Institute for Genomic Research-Multi Experiment Viewer(MeV) tool. Differentially expressed miRNAs that were found to be statistically significant (with parameters, fold change ≥2.0, and FDR=0 for MeV-SAM analysis) were identified as the potential miRNA candidates.
2021-07-28 | E-MTAB-9140 | biostudies-arrayexpress
Project description:Whole exome and transcriptome sequencing in sporadic ALS
| PRJNA247709 | ENA
Project description:Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS.
2015-07-19 | GSE67196 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of a disease spectrum with shared clinical, genetic and pathological features. These include near ubiquitous pathological inclusions of the RNA binding protein (RBP) TDP-43, and often the presence of a GGGGCC expansion in the C9ORF72 (C9) gene. Here we show unexpectedly that the signature of hnRNP H sequestration and altered splicing of target transcripts we identified in C9ALS patients (Conlon et al. 2016) also occurs in fully half of 50 post-mortem sporadic, non-C9 ALS/FTD post-mortem brains. Furthermore, and equally surprisingly, these “like-C9” brains also contained correspondingly high amounts of insoluble TDP-43, as well as several other disease-related RBPs, and this correlates with widespread global splicing defects. Finally, we show that the like-C9 sporadic patients, like actual C9ALS patients, were much more likely to have developed FTD. We propose that these unexpected links between C9 and sporadic ALS/FTD define a common mechanism in this disease spectrum.
2018-07-13 | GSE116622 | GEO
Project description:Differentiated motor neurons from hiPSC derived from peripheral nerve fibroblasts of sporadic ALS patients and evaluated the gene expression profile by means microarray-linked to specific analysis tools.
2015-04-25 | GSE68240 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron death due to nuclear loss and cytoplasmic aggregation of the splice factor TDP-43. Pathologic TDP-43 associates with stress granules (SGs) and downregulating the SG-associated protein Ataxin-2 (Atxn2) using antisense oligonucleotides (ASOs) prolongs survival in the TAR4/4 sporadic ALS mouse model, a strategy that failed in clinical trials, likely due to inadequate target engagement. Here, we used an AAV with potent motor neuron transduction to deliver optimized Atxn2-targeting miRNAs. Atxn2 knockdown was achieved throughout the central nervous system (CNS) at a dose 40x lower than used in other work. In TAR4/4 mice, miAtxn2 treatment increased mean (54%) and median (45%) survival and robustly improved strength-related measures. There was a corresponding reduction of lower motor neuron death as well as reduced inflammatory markers in both motor cortex and spinal cord, and phosphorylated TDP-43 was reduced to wildtype levels. Transcriptome-wide dysregulation in the TAR4/4 model recapitulated ALS-associated gene signatures that were rescued after Atxn2 reduction, identifying therapeutic mechanisms and potential biomarkers for translation. Additionally, in slow progressing hemizygous mice, treatment slowed disease progression and in ALS patient-derived lower motor neurons, our vector transduced >95% of cells at an MOI 4 logs lower than previously reported for AAV and reduced human ATXN2 in a dose-dependent manner. Cumulatively these data support the utility of AAV-mediated RNAi against Atxn2 as a robust and translatable treatment strategy for sporadic ALS.
2025-05-15 | GSE283631 | GEO