MIR-186 is decreased in aged brain and suppresses BACE1 expression

Jaekwang Kim, Hyejin Yoon, Dah Eun Chung, Jennifer L. Brown, Krystal C. Belmonte, Jungsu Kim

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Accumulation of amyloid β (Aβ) in the brain is a key pathological hallmark of Alzheimer's disease (AD). Because aging is the most prominent risk factor for AD, understanding the molecular changes during aging is likely to provide critical insights into AD pathogenesis. However, studies on the role of miRNAs in aging and AD pathogenesis have only recently been initiated. Identifying miRNAs dysregulated by the aging process in the brain may lead to novel understanding of molecular mechanisms of AD pathogenesis. Here, we identified that miR-186 levels are gradually decreased in cortices of mouse brains during aging. In addition, we demonstrated that miR-186 suppresses β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression by directly targeting the 3′UTR of Bace1 mRNA in neuronal cells. In contrast, inhibition of endogenous miR-186 significantly increased BACE1 levels in neuronal cells. Importantly, miR-186 over-expression significantly decreased Aβ level by suppressing BACE1 expression in cells expressing human pathogenic mutant amyloid precursor protein. Taken together, our data demonstrate that miR-186 is a potent negative regulator of BACE1 in neuronal cells and it may be one of the molecular links between brain aging and the increased risk for AD during aging.

Original languageEnglish (US)
Pages (from-to)436-445
Number of pages10
JournalJournal of Neurochemistry
Volume137
Issue number3
DOIs
StatePublished - May 1 2016

Keywords

  • aging
  • Alzheimer's disease
  • BACE1
  • microRNA
  • MIR-186

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Kim, J., Yoon, H., Chung, D. E., Brown, J. L., Belmonte, K. C., & Kim, J. (2016). MIR-186 is decreased in aged brain and suppresses BACE1 expression. Journal of Neurochemistry, 137(3), 436-445. https://doi.org/10.1111/jnc.13507