title: Widespread microRNA dysregulation in multiple system atrophy - disease-related alteration in miR-96.
abstract: MicroRNA (miRNA) are short sequences of RNA that function as post-transcriptional regulators by binding to target mRNA transcripts resulting in translational repression. A number of recent studies have identified miRNA as being involved in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the role of miRNA in multiple system atrophy (MSA), a progressive neurodegenerative disorder characterized by oligodendroglial accumulation of alpha-synuclein remains unexamined. In this context, this study examined miRNA profiles in MSA cases compared with controls and in transgenic (tg) models of MSA compared with non-tg mice. The results demonstrate a widespread dysregulation of miRNA in MSA cases, which is recapitulated in the murine models. The study employed a cross-disease, cross-species approach to identify miRNA that were either specifically dysregulated in MSA or were commonly dysregulated in neurodegenerative conditions such as Alzheimer's disease, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration or the tg mouse model equivalents of these disorders. Using this approach we identified a number of miRNA that were commonly dysregulated between disorders and those that were disease-specific. Moreover, we identified miR-96 as being up-regulated in MSA. Consistent with the up-regulation of miR-96, mRNA and protein levels of members of the solute carrier protein family SLC1A1 and SLC6A6, miR-96 target genes, were down-regulated in MSA cases and a tg model of MSA. These results suggest that miR-96 dysregulation may play a role in MSA and its target genes may be involved in the pathogenesis of MSA.
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Kiren
authors.initials: K
authors.lastname: Ubhi
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Kragh
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Inglis
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Michael
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, 92093-0624, USA.|Department of Pathology, University of California, La Jolla, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D016022:Case-Control Studies; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000099247:Taurine Transporters
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D000099247:Taurine Transporters; C541492:MIRN96 microRNA, human; C541554:Mirn96 microRNA, mouse
keywords: human; mouse; neurodegeneration; transgenic