期刊
NEUROREPORT
卷 24, 期 6, 页码 318-323出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0b013e32835fb6b0
关键词
Alzheimer's disease; amyloidosis; hippocampal CA1; innate immune response; microglial cells; miRNA-34a; NF-kappa B; phagocytosis; TREM2
资金
- LSUHSC
- Alzheimer Association [IIRG-09-131729]
- NIA [AG18031, AG038834]
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-kappa B (NF-kappa B)-sensitive miRNA-34a (encoded at chr1p36.22), upregulated in Alzheimer's disease, was found to target the 299 nucleotide human TREM2 mRNA 30-untranslated region (30-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-kappa B-mediated, miRNA-34a-regulated downregulation of TREM2 expression may shape innate immune and phagocytic responses that contribute to inflammatory neurodegeneration. NeuroReport 24:318-323 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据