Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8478499 | Molecular and Cellular Neuroscience | 2016 | 50 Pages |
Abstract
Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis.
Keywords
TYRP1C9orf72ReelinCRYMCD4RELNDGCR8AQP1SALSTDP-43PACTKIF5AUBQLN2TAR DNA binding protein 43chemokine C-C motif ligand 2ubiquilin 2Differentially expressed microRNAFASCCL2PBMCqPCRFDRGAPDHFUscycle thresholdaquaporin 1amyotrophic lateral sclerosisSporadic amyotrophic lateral sclerosisfamilial amyotrophic lateral sclerosisEpigeneticsAlzheimer's diseaseALSParkinson's diseaseTAMfALSRISCCluster of differentiation 4fused in sarcomaDAVIDreverse transcriptionPeripheral blood mononuclear cellDEGRNA Induced Silencing ComplexUTR یا untranslated regions untranslated regionfalse discovery rateMicroRNAMiRNAGene ontologyquantitative polymerase chain reactionDatabase for Annotation, Visualization, and Integrated Discoverytyrosinase-related protein 1Differentially expressed genechromosome 9 open reading frame 72glyceraldehyde-3-phosphate dehydrogenase
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Authors
Claudia Figueroa-Romero, Junguk Hur, J. Simon Lunn, Ximena Paez-Colasante, Diane E. Bender, Raymond Yung, Stacey A. Sakowski, Eva L. Feldman,