1 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 Section IV. Building 22.4/24.4, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 LUKKET: Wilhelm Johannsen Center, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular events throughout the development of the human brain. Recent studies have identified a molecular and ultimately pathogenic role for a subset of miRNAs in Alzheimer's disease and schizophrenia, including the characterization of their downstream CNS mRNA targets, such as beta-secretase (BACE1) and calmodulin-dependent protein kinase II (CaMKII). Here, we present an overview of the current progress in miRNA research related to CNS disorders and also highlight the utility of LNA (locked nucleic acid)-modified oligonucleotides in the detection and modulation of miRNA activity.
Neuromolecular Medicine, 2009, Vol 11, Issue 3, p. 162-72