title: MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer's Disease (AD)-Novel and Unique Pathological Features.
abstract: Of the approximately ~2.65 × 10³ mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset-about 35-40-are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA-mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer's disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.
authors.affiliation: Louisiana State University Neuroscience Center, LSU Health Sciences Center, New Orleans, LA 70112, USA. yzhao4@lsuhsc.edu.|Department of Anatomy and Cell Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. yzhao4@lsuhsc.edu.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Alchem Biotek, Toronto, ON M5S 1A8, Canada. wlukiw@yahoo.com.
authors.forename: Aileen I
authors.initials: AI
authors.lastname: Pogue
authors.affiliation: Louisiana State University Neuroscience Center, LSU Health Sciences Center, New Orleans, LA 70112, USA. wlukiw@lsuhsc.edu.|Alchem Biotek, Toronto, ON M5S 1A8, Canada. wlukiw@lsuhsc.edu.|Department of Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. wlukiw@lsuhsc.edu.|Department of Neurology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. wlukiw@lsuhsc.edu.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Lukiw
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger
keywords: Aβ42 peptide; age-related macular degeneration (AMD); amyloid clearance; heterogeneity of the disease process; inflammation; innate-immune response; miRNA-125b; miRNA-146a; miRNA-155; miRNA-34a; miRNA-7; miRNA-9; microRNA (miRNA); normal aging; prion disease; sporadic AD