Int J Biochem Mol Biol 2012;3(1):105-116
Review Article
Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in
Alzheimer’s disease (AD) and in age-related macular degeneration (AMD)
Walter J Lukiw, Bhattacharjee Surjyadipta, Prerna Dua, Peter N Alexandrov
LSU Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans LA 70112, USA;
Department of Health Information Management, Louisiana Technical University, Ruston, LA 71272, USA; Russian Academy of Medical
Sciences, Moscow 113152, RUSSIA
Received March 10, 2012; accepted March 18, 2012; Epub March 20, 2012; Published March 30, 2012
Abstract: Alzheimer’s disease (AD) and age-related macular degeneration (AMD) are complex and progressive inflammatory degenerations of
the human neocortex and retina. Recent molecular, genetic and epigenetic evidence indicate that at least 4 micro RNAs (miRNAs) - including
the NF-кB-regulated miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 - are progressively up-regulated in both AD and AMD. This quartet
of up-regulated miRNAs in turn down-regulate a small brain- and retinal-cell-relevant family of target mRNAs, including that encoding
complement factor H (CFH), a major negative regulator of the innate immune and inflammatory response. Together miRNA-146a and miRNA-
155 recognize an overlapping miRNA regulatory control (MiRC) region in the CFH 3’-untranslated region (3’-UTR; 5’-TTTAGTATTAA-3’) to which
either of these miRNAs may interact. Progressive, pathogenic increases in specific miRNA binding to the entire 232 nucleotide CFH 3’-UTR
appears to be a major regulator of CFH expression down-regulation, and the inflammatory pathology that characterizes both AMD and AD. The
data presented in this review provides evidence that up-regulation of brain- and retinal- abundant miRNAs, including miRNA-9, miRNA-125b,
miRNA-146a and miRNA-155, are common to the pathogenetic mechanism of CFH deficiency that drives inflammatory neurodegeneration,
and for the first time indicates multiple, independent miRNA-mediated regulation of the CFH mRNA 3’-UTR. (IJBMB1203003).
Keywords: Brain, complement factor H, evolution, miRNA regulatory control (MiRC) region, micro RNA, miRNA-9, miRNA-125b, miRNA-146a,
miRNA-155, retina, small non-coding RNA
Address all correspondence to:
Dr. WJ Lukiw
Ophthalmology and Human Genetics
LSU Neuroscience Center of Excellence
Louisiana State University Health Sciences Center
2020 Gravier Street, Suite 904
New Orleans, LA 70112-2272, USA.
Tel: 504-599-0842; Fax: 504-568-5801
E-mail: wlukiw@ lsuhsc.edu
Review Article
Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in
Alzheimer’s disease (AD) and in age-related macular degeneration (AMD)
Walter J Lukiw, Bhattacharjee Surjyadipta, Prerna Dua, Peter N Alexandrov
LSU Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans LA 70112, USA;
Department of Health Information Management, Louisiana Technical University, Ruston, LA 71272, USA; Russian Academy of Medical
Sciences, Moscow 113152, RUSSIA
Received March 10, 2012; accepted March 18, 2012; Epub March 20, 2012; Published March 30, 2012
Abstract: Alzheimer’s disease (AD) and age-related macular degeneration (AMD) are complex and progressive inflammatory degenerations of
the human neocortex and retina. Recent molecular, genetic and epigenetic evidence indicate that at least 4 micro RNAs (miRNAs) - including
the NF-кB-regulated miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 - are progressively up-regulated in both AD and AMD. This quartet
of up-regulated miRNAs in turn down-regulate a small brain- and retinal-cell-relevant family of target mRNAs, including that encoding
complement factor H (CFH), a major negative regulator of the innate immune and inflammatory response. Together miRNA-146a and miRNA-
155 recognize an overlapping miRNA regulatory control (MiRC) region in the CFH 3’-untranslated region (3’-UTR; 5’-TTTAGTATTAA-3’) to which
either of these miRNAs may interact. Progressive, pathogenic increases in specific miRNA binding to the entire 232 nucleotide CFH 3’-UTR
appears to be a major regulator of CFH expression down-regulation, and the inflammatory pathology that characterizes both AMD and AD. The
data presented in this review provides evidence that up-regulation of brain- and retinal- abundant miRNAs, including miRNA-9, miRNA-125b,
miRNA-146a and miRNA-155, are common to the pathogenetic mechanism of CFH deficiency that drives inflammatory neurodegeneration,
and for the first time indicates multiple, independent miRNA-mediated regulation of the CFH mRNA 3’-UTR. (IJBMB1203003).
Keywords: Brain, complement factor H, evolution, miRNA regulatory control (MiRC) region, micro RNA, miRNA-9, miRNA-125b, miRNA-146a,
miRNA-155, retina, small non-coding RNA
Address all correspondence to:
Dr. WJ Lukiw
Ophthalmology and Human Genetics
LSU Neuroscience Center of Excellence
Louisiana State University Health Sciences Center
2020 Gravier Street, Suite 904
New Orleans, LA 70112-2272, USA.
Tel: 504-599-0842; Fax: 504-568-5801
E-mail: wlukiw@ lsuhsc.edu
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