Anti-inflammatory regulator CFH is decreased by miRNA fragment, according to article in Journal of Biological Chemistry.
Researchers in the Neuroscience Center of Excellence at the LSU Health Sciences Center New Orleans have shown that a miniscule piece of miRNA-146a is found in increased amounts in stressed human brain cells and in Alzheimer’s disease, and that it plays a crucial role in the regulation of inflammation and disease-related neuropathology thought to be integral to the Alzheimer’s disease process.
Testing both control cells and Alzheimer’s disease-affected tissues, the team found that miRNA-146a targets the messenger RNA of important anti-inflammatory regulator complement factor H (CFH) by reducing the amount and bioavailability of CFH, contributing to the development of Alzheimer’s disease.
Within human Alzheimer’s disease brain cells in primary culture, investigators distinguished a specific upregulation of the NF- B-sensitive miRNA-146a, highly complementary to the 3′-untranslated region of CFH.
Transfection of human neural (HN) cells showed significant upregulation of luciferase activity that paralleled decreases in CFH gene expression. Treatment of stressed HN cells with the NF- B inhibitor pyrollidine dithiocarbamate or the resveratrol analog CAY10512 then ended that response.
The paper is published in the November 14, 2008 issue of The Journal of Biological Chemistry.
