Document Detail


Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a.
MedLine Citation:
PMID:  23462268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease. In this study, we provide evidence that TREM2 is downregulated in samples of sporadic Alzheimer hippocampal CA1 compared with age-matched controls. A nuclear factor-кB (NF-кB)-sensitive miRNA-34a (encoded at chr1p36.22), upregulated in Alzheimer's disease, was found to target the 299 nucleotide human TREM2 mRNA 3'-untranslated region (3'-UTR) and downregulate the expression of a TREM2-3'-UTR reporter vector. A stabilized anti-miRNA-34a (AM-34a) quenched this pathogenic response. The results suggest that an epigenetic mechanism involving an NF-кB-mediated, miRNA-34a-regulated downregulation of TREM2 expression may shape innate immune and phagocytic responses that contribute to inflammatory neurodegeneration.
Authors:
Yuhai Zhao; Surjyadipta Bhattacharjee; Brandon M Jones; Prerna Dua; Peter N Alexandrov; James M Hill; Walter J Lukiw
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Neuroreport     Volume:  24     ISSN:  1473-558X     ISO Abbreviation:  Neuroreport     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-22     Completed Date:  2013-09-17     Revised Date:  2014-08-15    
Medline Journal Info:
Nlm Unique ID:  9100935     Medline TA:  Neuroreport     Country:  England    
Other Details:
Languages:  eng     Pagination:  318-23     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions / genetics
Alzheimer Disease / metabolism
Animals
Blotting, Northern
Blotting, Western
Cells, Cultured
Data Interpretation, Statistical
Down-Regulation / drug effects
Epigenesis, Genetic
Hippocampus / cytology,  drug effects,  metabolism
Inflammation / pathology
Membrane Glycoproteins / biosynthesis,  genetics*
Mice
Mice, Inbred C3H
MicroRNAs / biosynthesis,  genetics*,  metabolism
Microglia / metabolism
NF-kappa B / genetics*,  physiology
Phagocytosis / physiology
Quality Control
Receptors, Immunologic / biosynthesis,  genetics*
Grant Support
ID/Acronym/Agency:
AG038834/AG/NIA NIH HHS; AG18031/AG/NIA NIH HHS; P50 AG016573/AG/NIA NIH HHS; P50 AG16573/AG/NIA NIH HHS; R01 AG018031/AG/NIA NIH HHS; R01 AG038834/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/MIRN34 microRNA, mouse; 0/Membrane Glycoproteins; 0/MicroRNAs; 0/NF-kappa B; 0/Receptors, Immunologic; 0/Trem2 protein, mouse
Comments/Corrections

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