Altered Purkinje cell miRNA expression and SCA1 pathogenesis

NEUROBIOLOGY OF DISEASE

卷:54

Article

Rodriguez-Lebron, Edgardo¹  Liu, Gumei^1,4  Keiser, Megan⁴  Behlke, Mark A.⁵  Davidson, Beverly L.^1,2,3,4 

[1] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA

[2] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA

[3] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA

[4] Univ Iowa, Dept Neurosci, Iowa City, IA 52242 USA

[5] Integrated DNA Technol Inc, Coralville, IA 52241 USA

关键词: Spinocerebellar ataxia;    Polyglutamine;    Ataxin-1;    miRNA;    miR-150;    Vegfa;    RNA interference;    AAV;    Cerebellum;    Neurodegeneration;   

DOI  :  10.1016/j.nbd.2013.01.019

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Inc.

【 授权许可】

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