Spreading of Alzheimer's disease inflammatory signaling through soluble micro-RNA.
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.
Department of Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112-2272, USA. wlukiw@lsuhsc.edu
Walter J
WJ
Lukiw
Peter N
PN
Alexandrov
Yuhai
Y
Zhao
James M
JM
Hill
Surjyadipta
S
Bhattacharjee
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D012995:Solubility
D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs