3-B-P-057 〇木下 千智¹、鈴木 亮²、青山 晃治¹ Chisato Kinoshita¹, Ryo Suzuki², Koji Aoyama^{1 1}帝京大・医、²帝京大・薬 ¹Teikyo Univ. Sch. Med., ²Teikyo Univ. Fac. Pharm. Sci. Glutathione (GSH) is an important antioxidant that plays a critical role in neuroprotection. Neuronal GSH depletion induces oxidative stress causing some neurodegenerative diseases. The neuronal GSH levels are mainly regulated by excitatory amino acid carrier 1 (EAAC1) and its inhibitory protein, glutamate transporter-associated protein 3-18 (GTRAP3-18). In this study, we found that GTRAP3-18 levels were increased by the up-regulation of the miR-96-5p, which is a microRNA reported to decrease EAAC1 levels in neurons. We also discovered that neuro-oncological ventral antigen 1 (NOVA1) is an intermediate protein for GTRAP3-18 expression via miR-96-5p. We show that the intra-arterial administration of a miR-96-5p-inhibiting nucleic acid to living mice by a drug delivery system using microbubbles and ultrasound decreased the levels of GTRAP3-18 via NOVA1, while increased the levels of both EAAC1 and GSH in the mouse brain. NOVA1 was recognized as an RNA-binding protein involved in miRNA regulation as well as mRNA processing and splicing. Analysis of RNA-fold predictions shows that the predicted NOVA1-binding site on GTRAP3-18 3'-UTR is a stem-loop structure, and that the stem sequence is a target site of some miRNAs, implying that NOVA1 binds to the 3'-UTR of target genes and induces conformational changes in the RNA structure that favor association with miRNAs. These findings suggest that the delivery of a miR-96-5p inhibitor to the brain would efficiently increase the neuroprotective activity by increasing GSH levels via EAAC1, GTRAP3-18 and NOVA1.