hsa-miR-146a

Alzheimer's disease

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

CFH

Validated targets of miRNA from TarBase:

unknown : More...

Description:

Here we provide evidence in AD brains of a specific up-regulation of an NF-kB-sensitive miRNA-146a highly complementary to the 3' un-translated region (3'UTR) of complement factor H (CFH), an important repressor of the brain's inflammatory response. Up-regulation of miRNA-146a coupled to down-regulation of CFH was observed in AD brain and in IL-1ss, Ass42 and/or oxidatively-stressed human neural (HN) cells in primary culture. Transfection of HN cells using an NF-kB-containing pre-miRNA-146a promoter-luciferase reporter construct in stressed HN cells showed significant up-regulation of luciferase activity that paralleled decreases in CFH gene expression. Treatment of stressed HN cells with the NF-kB inhibitors pyrollidine dithiocarbamate (PDTC) or the resveratrol analog CAY10512 abrogated this response. Incubation of an antisense oligonucleotide to miRNA-146a (anti-miRNA-146a; AM146a) was found to restore CFH expression levels. These data indicate that NF-kB-sensitive miRNA-146a-mediated modulation of CFH gene expression may in part regulate an inflammatory response in AD brain and in stressed HN cell models of AD, and illustrates the potential for anti-miRNAs as an effective therapeutic strategy against pathogenic inflammatory signaling.

Reference:

An NF-kB-sensitive microRNA-146a-mediated inflammatory circuit in Alzheimer's disease and in stressed human brain cells. | PMID:18801740
Lukiw WJ, Zhao Y, Cui JG.
J Biol Chem. 2008 Sep 18. [Epub ahead of print]