title: Prevention of Lymphocyte Neurotoxic Effects by microRNA Delivery.
abstract: Aicardi Goutieres Syndrome (AGS) is characterized by mutations occurring in genes encoding RNAses. AGS mutations silence intracellular RNases resulting in an intracellular overload of short RNAs arresting the physiological production of microRNA required for brain development. MiR-219 is typically down-regulated in Aicardi Goutieres Syn-drome (AGS). The goal of this study is to investigate miR-219 role in protecting astrocytes co-cultured with AGS-mutated lymphocytes. These lymphocytes display neurotoxic properties due to the presence of AGS-mutation and to their activa-tion by interpheron-alpha (IFN). Obtained results provide the evidence that astrocytes transfected with microRNA-219 are protected from the neurotoxic action of AGS lymphocytes activated by IFN-alpha. In particular, the miR-219 transfection increased astrocyte viability, growth, and differentiation while decreasing cell necrosis and apoptosis. Thus, microRNA-219 transfection is a valuable strategy in order to confer resistance to astrocytes towards lymphocyte-induced neurotoxici-ty especially in the presence of IFN-alpha, whose levels are typically increased in the cerebrospinal fluid of AGS patients.
authors: Alessandra
authors: A
authors: Pulliero
authors: Barbara
authors: B
authors: Marengo
authors: Daniela
authors: D
authors: Fenoglio
authors: Alessia
authors: A
authors: Parodi
authors: Cristina
authors: C
authors: Cereda
authors: Cinzia
authors: C
authors: Domenicotti
authors: Simona
authors: S
authors: Orcesi
authors: Jessica
authors: J
authors: Galli
authors: Ivana
authors: I
authors: Olivieri
authors: Gilberto
authors: G
authors: Filaci
authors: Umberto
authors: U
authors: Balottin
authors: Elisa
authors: E
authors: Fazzi
authors: Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132, Genoa, Italy.
authors: Alberto
authors: A
authors: Izzotti
mesh_terms: D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology*; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics*; D018920:Coculture Techniques; D006801:Humans; D016898:Interferon-alpha; D008214:Lymphocytes; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009336:Necrosis; D009421:Nervous System Malformations / Q000235:genetics*; D012260:Ribonucleases / Q000235:genetics; D014162:Transfection
chemical_list: D016898:Interferon-alpha; C578248:MIRN219 microRNA, human; D035683:MicroRNAs; D012260:Ribonucleases