PMID- 29738527
OWN - NLM
STAT- MEDLINE
DCOM- 20180801
LR  - 20240325
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 5
DP  - 2018
TI  - Defensive effect of microRNA-200b/c against amyloid-beta peptide-induced toxicity 
      in Alzheimer's disease models.
PG  - e0196929
LID - 10.1371/journal.pone.0196929 [doi]
LID - e0196929
AB  - MiRNA molecules are important post-transcriptional regulators of gene expression 
      in the brain function. Altered miRNA profiles could represent a defensive 
      response against the pathogenesis of neurodegenerative disorders, such as 
      Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other 
      gene silencing methods, thus enhancing the expression of defensive miRNA could be 
      an effective therapy. However, little is known about the potential of targeting 
      miRNAs for the treatment of AD. Here, we examined the function of the miR-200 
      family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray 
      analysis of cortical tissue from Tg2576 transgenic mice. In murine primary 
      neurons, we found that upregulation of miR-200b or -200c was induced by the 
      addition of amyloid beta (Abeta). Neurons transfected with miR-200b or -200c reduced 
      secretion of Abeta in conditioned medium. Moreover, mice infused with miR-200b/c 
      into the brain were relieved of memory impairments induced by 
      intracerebroventricular injection of oligomeric Abeta, and demonstrated proper 
      spatial learning in the Barnes maze. To gain further understanding of the 
      relationship between miR-200b/c and Abeta, we identified target mRNAs via an 
      RNA-binding protein immunoprecipitation-microarray assay. Western blot analysis 
      showed that expression of ribosomal protein S6 kinase B1 (S6K1), a candidate 
      target, was inhibited by miR-200c. S6K1, a downstream effector of mammalian 
      target of rapamycin (mTOR), serves as a negative feedback mediator that 
      phosphorylates insulin receptor substrate 1 at serine residues (IRS-1pSer). 
      S6K1-dependent IRS-1pSer suppresses insulin signaling leading to insulin 
      resistance, which is frequently observed in AD brains. Notably, miR-200b/c 
      transfection of SH-SY5Y cells reduced the levels of IRS-1pSer. This finding 
      indicates that miR-200b/c has the potential to alleviate insulin resistance via 
      modulation of S6K1. Taken together, miR-200b/c may contribute to reduce Abeta 
      secretion and Abeta-induced cognitive impairment by promoting insulin signaling.
FAU - Higaki, Sayuri
AU  - Higaki S
AUID- ORCID: 0000-0003-1826-3848
AD  - Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, 
      Aichi, Japan.
FAU - Muramatsu, Masashi
AU  - Muramatsu M
AD  - Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, 
      Aichi, Japan.
AD  - Division of Phenotype Disease Analysis, Institute of Resource Development and 
      Analysis, Kumamoto University, Kumamoto, Japan.
FAU - Matsuda, Akio
AU  - Matsuda A
AD  - Department of Allergy and Clinical Immunology, National Research Institute for 
      Child Health and Development, Setagaya-ku, Tokyo, Japan.
FAU - Matsumoto, Kenji
AU  - Matsumoto K
AD  - Department of Allergy and Clinical Immunology, National Research Institute for 
      Child Health and Development, Setagaya-ku, Tokyo, Japan.
FAU - Satoh, Jun-Ichi
AU  - Satoh JI
AD  - Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical 
      University, Kiyose, Tokyo, Japan.
FAU - Michikawa, Makoto
AU  - Michikawa M
AD  - Department of Biochemistry, Nagoya City University Graduate School of Medical 
      Sciences, Nagoya, Aichi, Japan.
FAU - Niida, Shumpei
AU  - Niida S
AD  - Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, 
      Aichi, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180508
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (MIRN200 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
SB  - IM
MH  - Alzheimer Disease/*genetics/pathology
MH  - Amyloid beta-Peptides/administration & dosage/genetics
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Cognitive Dysfunction/genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Infusions, Intraventricular
MH  - Insulin Receptor Substrate Proteins/*genetics
MH  - Memory Disorders/genetics/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - MicroRNAs/*genetics
MH  - Neurons/metabolism/pathology
MH  - Ribosomal Protein S6 Kinases, 90-kDa/*genetics
MH  - Signal Transduction
PMC - PMC5940223
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/05/09 06:00
MHDA- 2018/08/02 06:00
PMCR- 2018/05/08
CRDT- 2018/05/09 06:00
PHST- 2018/01/15 00:00 [received]
PHST- 2018/04/23 00:00 [accepted]
PHST- 2018/05/09 06:00 [entrez]
PHST- 2018/05/09 06:00 [pubmed]
PHST- 2018/08/02 06:00 [medline]
PHST- 2018/05/08 00:00 [pmc-release]
AID - PONE-D-18-01399 [pii]
AID - 10.1371/journal.pone.0196929 [doi]
PST - epublish
SO  - PLoS One. 2018 May 8;13(5):e0196929. doi: 10.1371/journal.pone.0196929. 
      eCollection 2018.