title: Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities.
abstract: Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington's and Parkinson's diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases. The encouraging results from recent clinical trials allow envisioning that pharmacological approaches based on miRNAs might, in a near future, reach the requirements for successful therapeutic outcomes and will improve the healthcare of patients with brain injuries or disorders. This review will focus on the current strategies used to modulate pharmacological function of miRNA using chemically modified oligonucleotides. We will then review the recent literature on strategies to improve nucleic acid delivery across the blood-brain barrier which remains a severe obstacle to the widespread application of miRNA therapeutics to treat brain diseases. Finally, we provide a state-of-art of current preclinical research performed in animal models for the treatment of neurocognitive disorders using miRNA as therapeutic agents and discuss future developments of miRNA therapeutics.
authors.forename: Viorel
authors.initials: V
authors.lastname: Simion
authors.forename: Wissem Deraredj
authors.initials: WD
authors.lastname: Nadim
authors.forename: Helene
authors.initials: H
authors.lastname: Benedetti
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
authors.forename: Severine
authors.initials: S
authors.lastname: Morisset-Lopez
authors.affiliation: Centre de Biophysique Moleculaire, CNRS UPR4301, Universite d&#39;Orleans France, 45071 Orleans Cedex, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baril
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D000070416:Antagomirs; D035683:MicroRNAs