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miR‐186 is decreased in aged brain and suppresses BACE 1 expression
Author(s) -
Kim Jaekwang,
Yoon Hyejin,
Chung Daheun,
Brown Jennifer L.,
Belmonte Krystal C,
Kim Jungsu
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13507
Subject(s) - pathogenesis , amyloid precursor protein , microrna , regulator , microbiology and biotechnology , biology , amyloid precursor protein secretase , endogeny , alzheimer's disease , mutant , downregulation and upregulation , bace1 as , neuroscience , medicine , endocrinology , gene , biochemistry , disease , immunology
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 mi RNA s in aging and AD pathogenesis have only recently been initiated. Identifying mi RNA s 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 ( BACE 1) expression by directly targeting the 3′ UTR of Bace1 mRNA in neuronal cells. In contrast, inhibition of endogenous miR‐186 significantly increased BACE 1 levels in neuronal cells. Importantly, miR‐186 over‐expression significantly decreased Aβ level by suppressing BACE 1 expression in cells expressing human pathogenic mutant amyloid precursor protein. Taken together, our data demonstrate that miR‐186 is a potent negative regulator of BACE 1 in neuronal cells and it may be one of the molecular links between brain aging and the increased risk for AD during aging.We identified that miR‐186 levels are gradually decreased in mouse cortices during aging. Furthermore, we demonstrated that miR‐186 is a novel negative regulator of beta‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) expression in neuronal cells. Therefore, we proposed that reduction in miR‐186 levels during aging may lead to the up‐regulation of BACE1 in the brain, thereby increasing a risk for Alzheimer's disease in aged individuals. Read the Editorial Highlight for this article on page 308.