title: The Yin and Yang of nucleic acid-based therapy in the brain.
abstract: The post-genomic era has unveiled the existence of a large repertory of non-coding RNAs and repetitive elements that play a fundamental role in cellular homeostasis and dysfunction. These may represent unprecedented opportunities to modify gene expression at the right time in the correct space in vivo, providing an almost unlimited reservoir of new potential pharmacological agents. Hijacking their mode of actions, the druggable genome can be extended to regulatory RNAs and DNA elements in a scalable fashion. Here, we discuss the state-of-the-art of nucleic acid-based drugs to treat neurodegenerative diseases. Beneficial effects can be obtained by inhibiting (Yin) and increasing (Yang) gene expression, depending on the disease and the drug target. Together with the description of the current use of inhibitory RNAs (small inhibitory RNAs and antisense oligonucleotides) in animal models and clinical trials, we discuss the molecular basis and applications of new classes of activatory RNAs at transcriptional (RNAa) and translational (SINEUP) levels.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia (IIT), Genova, Italy; Area of Neuroscience, SISSA, Trieste, Italy. Electronic address: stefano.gustincich@iit.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy; Department of Health Sciences, Universita' del Piemonte Orientale, Novara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchelli
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mallamaci
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D009696:Nucleic Acids / Q000494:pharmacology*
chemical_list: D009696:Nucleic Acids
keywords: Antisense oligonucleotide; Brain; NMHV; Neurodegenerative disease; Non-coding RNA; Nucleic-acid therapy; RNA activation; SINEUP; Small inhibitory RNA