Studying micro RNA function and dysfunction in Alzheimer’s disease
- 1Department of Neurology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- 2Department of Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- 3Department of Genomics and Human Genetics, Russian Academy of Medical Science, Vavilov Institute of General Genetics, Moscow, Russia
- 4Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA
- 5Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia
Alzheimer’s disease (AD) is a tragic, progressive, age-related neurological dysfunction, representing one of the most prevalent neurodegenerative disorders in industrialized societies. Globally, 5 million new cases of AD are diagnosed annually, with one new AD case being reported every 7 s. Most recently there has been a surge in the study of the regulatory mechanisms of the AD process, and the particular significance of small non-coding ∼22 ribonucleotide RNAs called micro RNAs (miRNAs). Abundant data have profiled miRNA patterns in healthy, aging brain, in mild cognitive impairment (MCI), and in the moderate- and late-stages of AD. The major mode of action of miRNA is to interact, via base-pair complementarity, with ribonucleotides located within the 3′ untranslated region (3′-UTR) of multiple target messenger RNAs (mRNAs), and in doing so decrease the capability of that specific mRNA to be expressed. Many miRNAs are highly cell- and tissue-specific. The human brain appears to use only a highly specific fraction of all known human miRNAs, whose speciation and complexity are defined as a discrete subset of all known small non-coding RNAs (sncRNAs) in the brain. In general, in contrast to normally, aging human brain, in AD a family of pathogenically up-regulated miRNAs appear to be down-regulating the expression certain brain-essential mRNA targets, including key regulatory genes involved interactively in neuroinflammation, synaptogenesis, neurotrophic functions, and amyloidogenesis. These up-regulated, NF-kB-sensitive miRNAs, involved in the innate immune and inflammatory response and synaptic, neurotrophic, and amyloidogenic functions include miRNA-9, miRNA-125b, miRNA-146a, and miRNA-155. Other miRNAs of the miRNA-15/107 family, miRNA-153 and miRNA-190, and others, will be discussed. Overall, this manuscript will review the known contribution of miRNAs to aging brain function and the role they appear to play in the incidence and progression of AD.
Keywords: aging, Alzheimer’s disease, amyloidogenesis, inflammation, miRNA, neurotrophism, presenilin, synaptogenesis
Citation: Lukiw WJ, Andreeva TV, Grigorenko AP and Rogaev EI (2013) Studying micro RNA function and dysfunction in Alzheimer’s disease. Front. Gene. 3:327. doi: 10.3389/fgene.2012.00327
Received: 06 November 2012; Accepted: 28 December 2012;
Published online: 06 February 2013.
Edited by:Peng Jin, Emory University School of Medicine, USA
Reviewed by:Timothy Bowen, Cardiff University, UK
Hongyan Xu, Georgia Health Sciences University, USA
Copyright: © 2013 Lukiw, Andreeva, Grigorenko and Rogaev. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Walter J. Lukiw, Departments of Neurology and Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. e-mail: email@example.com; Evgeny I. Rogaev, University of Massachusetts Medical School, BNRI, 303 Belmont Street, Worcester, MA 01604, USA. e-mail: firstname.lastname@example.org