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MicroRNA 486 is a potentially novel target for the treatment of spinal cord injury

Jee, Min Ki, Jung, Jin Sun, Choi, Jee In, Jang, Jin Ah, Kang, Kyung Sun, Im, Young Bin, Kang, Soo Kyung·2012·Brain
DOI 10.1093/brain/aws047
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Abstract

MicroRNAs have been shown to effectively regulate gene expression at the translational level. Recently, we identified novel microRNAs that were upregulated in a mouse model of spinal cord injury. Among those, we have focused on microRNA 486, which directly represses NeuroD6 expression through a conserved sequence in its untranslated region. We correlated the overexpression of microRNA 486 in motor neurons with a poor outcome due to progressive neurodegeneration and a pathophysiology that is mediated by reactive oxygen species. The expression of microRNA 486 was induced by reactive oxygen species that were produced by inflammatory factors, and reactive oxygen species were accumulated in response to the knockdown of NeuroD6, which enhances the downregulation of glutathione peroxidase 3 and thioredoxin-like 1 after traumatic spinal cord injury. NeuroD6 directly bound to regulatory regions of thioredoxin-like 1 and glutathione peroxidase 3 in motor neurons and activated their expression, which promoted reactive oxygen species scavenging. Moreover, knocking down microRNA 486 induced the expression of NeuroD6, which effectively ameliorated the spinal cord injury and allowed the mice to recover motor function. The infusion of exogenic NeuroD6 in spinal cord injury lesions effectively blocked apoptosis by reactivating thioredoxin-like 1 and glutathione peroxidase 3, which was accompanied by a recovery of motor function. Collectively, these findings have identified a novel microRNA in…

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Metadata

Authors
Jee, M. K., Jung, J. S., Choi, J. I., Jang, J. A., Kang, K. S., Im, Y. B., & Kang, S. K.
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2012-03-30
Volume
135
Issue
4
Pages
1237-1252
ISSN
  • 1460-2156
  • 0006-8950
DOI
10.1093/brain/aws047
Cited by
91
References
1
Language
en

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