Abstract:
:Cerebellar degeneration is a devastating manifestation of cerebellar-type multiple-system atrophy (MSA), a rapidly progressive neurodegenerative disease, and the exact pathogenesis is unknown. Here, we examined the expression of micro-RNAs (miRNAs), which are short noncoding RNAs, in the cerebellum of MSA and the key target genes. miRNA microarray found 11 miRNAs with significantly different expression in MSA cerebellum compared to cerebellum from age-, sex-, and postmortem interval-matched controls. miR-202 was the most upregulated in the MSA samples. In silico analysis, followed by target gene luciferase assay, in vitro transfection, and Western blotting in human samples showed that miR-202 downregulates Oct1 (Pou2f1), a transcription factor expressed in cerebellar Purkinje cells. Transfection of Neuro-2a cells with miR-202 enhanced oxidative stress-induced cell death, and an antagomir to miR-202 inhibited this effect of miR-202. This study provides novel insight into the role of miRNA in cerebellar degeneration and suggests that miR-202 is a key miRNA mediating the pathogenesis of MSA.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Lee ST,Chu K,Jung KH,Ban JJ,Im WS,Jo HY,Park JH,Lim JY,Shin JW,Moon J,Lee SK,Kim M,Roh JKdoi
10.1007/s12035-014-8788-4subject
Has Abstractpub_date
2015-02-01 00:00:00pages
180-6issue
1eissn
0893-7648issn
1559-1182journal_volume
51pub_type
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