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Widespread micro RNA dysregulation in multiple system atrophy – disease‐related alteration in miR‐96
Author(s) -
Ubhi Kiren,
Rockenstein Edward,
Kragh Christine,
Inglis Chandra,
Spencer Brian,
Michael Sarah,
Mante Michael,
Adame Anthony,
Galasko Douglas,
Masliah Eliezer
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12444
Subject(s) - progressive supranuclear palsy , microrna , corticobasal degeneration , biology , dementia with lewy bodies , context (archaeology) , disease , atrophy , neurodegeneration , dementia , medicine , gene , genetics , pathology , paleontology
Micro RNA (mi RNA ) 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 mi RNA as being involved in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the role of mi RNA in multiple system atrophy ( MSA ), a progressive neurodegenerative disorder characterized by oligodendroglial accumulation of alpha‐synuclein remains unexamined. In this context, this study examined mi RNA 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 mi RNA in MSA cases, which is recapitulated in the murine models. The study employed a cross‐disease, cross‐species approach to identify mi RNA 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 mi RNA 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 SLC 6A6, 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 .