hsa-miR-146a

Alzheimer's disease

Relationship type:

Unspecified

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:

Brain cells maintain distinct populations of miRNAs that support physiologically normal patterns of expression, however, certain miRNA abundances are significantly altered in neurodegenerative disorders such as Alzheimer's disease (AD). Here we provide evidence in human neural (HN) cells of an aluminum-sulfate- and reactive oxygen species (ROS)-mediated up-regulation of an NF-kappaB-sensitive miRNA-146a that down-regulates the expression of complement factor H (CFH), an important repressor of inflammation. This NF-kappaB-miRNA-146a-CFH signaling circuit is known to be similarly affected by Abeta42 peptides and in AD brain. These aluminum-sulfate-inducible events were not observed in parallel experiments using iron-, magnesium-, or zinc-sulfate-stressed HN cells. An NF-kappaB-containing miRNA-146a-promoter-luciferase reporter construct transfected into HN cells showed significant up-regulation of miRNA-146a after aluminum-sulfate treatment that corresponded to decreased CFH gene expression. These data suggest that (1) as in AD brain, NF-kappaB-sensitive, miRNA-146a-mediated, modulation of CFH gene expression may contribute to inflammatory responses in aluminum-stressed HN cells, and (2) underscores the potential of nanomolar aluminum to drive genotoxic mechanisms characteristic of neurodegenerative disease processes.

Reference:

Characterization of an NF-kappaB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells. | PMID:19540598
Pogue AI, Li YY, Cui JG, Zhao Y, Kruck TP, Percy ME, Tarr MA, Lukiw WJ.
J Inorg Biochem. 2009 May 24. [Epub ahead of print]