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Lukiw, Walter J.a,c; Alexandrov, Peter N.c; Zhao, Yuhaib; Hill, James M.a; Bhattacharjee, Surjyadiptaa
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.
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1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, Alzheimer's disease, digoxigenin, inflammatory neurodegeneration, locked nucleic acids, micro-RNA, miRNA-146a, miRNA-155, spreading
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