title: Altered Purkinje cell miRNA expression and SCA1 pathogenesis.
abstract: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder caused by polyglutamine repeat expansions in Ataxin-1. Recent evidence supports a role for microRNAs (miRNAs) deregulation in SCA1 pathogenesis. However, the extent to which miRNAs may modulate the onset, progression or severity of SCA1 remains largely unknown. In this study, we used a mouse model of SCA1 to determine if miRNAs are misregulated in pre- and post-symptomatic SCA1 cerebellum. We found a significant alteration in the steady-state levels of numerous miRNAs prior to and following phenotypic onset. In addition, we provide evidence that increased miR-150 levels in SCA1 Purkinje neurons may modulate disease pathogenesis by targeting the expression of Rgs8 and Vegfa.
authors: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors: Edgardo
authors: E
authors: Rodriguez-Lebron
authors: Gumei
authors: G
authors: Liu
authors: Megan
authors: M
authors: Keiser
authors: Mark A
authors: MA
authors: Behlke
authors: Beverly L
authors: BL
authors: Davidson
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011689:Purkinje Cells / Q000378:metabolism*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020710:RGS Proteins; C542368:RGS8 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
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