NeuroReport

Skip Navigation LinksHome > July 11, 2012 - Volume 23 - Issue 10 > Spreading of Alzheimer’s disease inflammatory signaling thro...
Neuroreport:
doi: 10.1097/WNR.0b013e32835542b0
Molecular Neuroscience

Spreading of Alzheimer’s disease inflammatory signaling through soluble micro-RNA

Lukiw, Walter J.a,c; Alexandrov, Peter N.c; Zhao, Yuhaib; Hill, James M.a; Bhattacharjee, Surjyadiptaa

Collapse Box

Abstract

Alzheimer’s disease is a progressive, neurodegenerative disorder that develops within the limbic system, spreading radially into anatomically linked brain association areas as the disease progresses. Analysis of temporal-lobe association of neocortex-derived extracellular fluid and cerebrospinal fluid from Alzheimer’s disease patients shows an abundant presence of micro-RNA (miRNA), including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly sensitive LED-Northern dot-blot focusing technique, we detected the secretion of potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155 was found to induce Alzheimer-type gene expression changes in control brain cells. These included downregulation in the expression of an important repressor of the innate immune response, complement factor H (CFH). These effects were neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may provide a novel and efficacious treatment to stem the miRNA-mediated spreading of inflammatory signaling involved in Alzheimer’s disease.

© 2012 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.