ArticleJournal of central nervous system disease2014
Molecular network analysis suggests a logical hypothesis for the pathological role of c9orf72 in amyotrophic lateral sclerosis/frontotemporal dementia.
Article in Journal of central nervous system disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Neuronal activity-dependent gene dysregulation inAmerican journal of physiology. Cell physiology · 2025Article
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.Nature communications · 2025Article
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.bioRxiv : the preprint server for biology · 2023Article
- Disease-associated astrocytes and microglia markers are upregulated in mice fed high fat diet.Scientific reports · 2023Article
- Review
- SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2021Article
- Repeat-associated non-AUG (RAN) translation mechanisms are running into focus for GGGGCC-repeat associated ALS/FTD.Progress in neurobiology · 2019Review
- eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated ALS.Acta neuropathologica communications · 2019Article
- TheMolecular and cellular biology · 2018Article
- Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS.Scientific reports · 2017Article
- Unraveling the Role of RNA Mediated Toxicity ofFrontiers in neuroscience · 2017Review
- Marked Differences in C9orf72 Methylation Status and Isoform Expression between C9/ALS Human Embryonic and Induced Pluripotent Stem Cells.Stem cell reports · 2016Article
- Modeling simple repeat expansion diseases with iPSC technology.Cellular and molecular life sciences : CMLS · 2016Review
- Cortical hyperexcitability in patients with C9ORF72 mutations: Relationship to phenotype.Muscle & nerve · 2016Article
- Old versus New Mechanisms in the Pathogenesis of ALS.Brain pathology (Zurich, Switzerland) · 2016Review
- RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord.PloS one · 2016Article
- A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease.Human molecular genetics · 2015Article
- Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases.Stem cells international · 2015Review
- Bioinformatics Data Mining Approach Suggests Coexpression of AGTPBP1 with an ALS-linked Gene C9orf72.Journal of central nervous system disease · 2015Article
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6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExpanded GGGGCC hexanucleotide repeats, ranging from hundreds to thousands in number, located in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene represent the most common genetic abnormality for familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (abbreviated as C9ALS). Currently, three pathological mechanisms, such as haplo insufficiency of C9orf72, formation of nuclear RNA foci composed of sense and antisense repeats, and accumulation of unconventionally transcribed dipeptide-repeat (DPR) proteins, are proposed for C9ALS. However, at present, the central mechanism underlying neurodegeneration in C9ALS remains largely unknown.
methodsBy using three distinct pathway analysis tools of bioinformatics, we studied molecular networks involved in C9ALS pathology by focusing on C9orf72 omics datasets, such as proteome of C9orf72 repeat RNA-binding proteins, transcriptome of induced pluripotent stem cells (iPSC)-derived motor neurons of patients with C9ALS, and transcriptome of purified motor neurons of patients with C9ALS.
resultsWe found that C9orf72 repeat RNA-binding proteins play a crucial role in the regulation of post-transcriptional RNA processing. The expression of a wide range of extracellular matrix proteins and matrix metalloproteinases was reduced in iPSC-derived motor neurons of patients with C9ALS. The regulation of RNA processing and cytoskeletal dynamics is disturbed in motor neurons of patients with C9ALS in vivo.
conclusionsBioinformatics data mining approach suggests a logical hypothesis that C9orf72 repeat expansions that deregulate post-transcriptional RNA processing disturb the homeostasis of cytoskeletal dynamics and remodeling of extracellular matrix, leading to degeneration of stress-vulnerable neurons in the brain and spinal cord of patients with C9ALS.
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