title: microRNAs in CNS disorders.
abstract: 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.
authors.affiliation: Department of Molecular and Integrative Neurosciences, Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Jannet
authors.initials: J
authors.lastname: Kocerha
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000033:anatomy & histology / Q000502:physiology; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020868:Gene Silencing; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D009696:Nucleic Acids