The effect of a miR-96-5p inhibitor delivery to brain using microbubbles and ultrasound technology on neuroprotection and autophagy activation
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- Kinoshita Chisato
- Teikyo Univ. Sch. Med. Dept. Pharm.
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- Aoyama Koji
- Teikyo Univ. Sch. Med. Dept. Pharm.
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- Suzuki Ryo
- Teikyo Univ. Fac. Pharm-Sci.
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- Matsumura Nobuko
- Teikyo Univ. Sch. Med. Dept. Pharm.
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- Omata Daiki
- Teikyo Univ. Fac. Pharm-Sci.
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- Maruyama Kazuo
- Teikyo Univ. Fac. Pharm-Sci.
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- Nakaki Toshio
- Teikyo Univ. Fac. Med. Tech.
Bibliographic Information
- Other Title
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- マイクロバブル超音波技術を用いたmiR-96-5p機能抑制薬の脳内送達によるによる神経保護作用とオートファジー活性化
Description
<p>Glutathione (GSH) is an important antioxidant that plays a critical role in neuroprotection. GSH depletion in neuron induces oxidative stress promoting neuronal damage, which is regarded as a hallmark of the early stage in some neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. 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 microRNA miR-96-5p, which has been reported to decrease EAAC1 levels in our previous study. We also discovered that neuro-oncological ventral antigen 1 (NOVA1) is an intermediate protein for GTRAP3-18 expression via miR-96-5p. Moreover, 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. Moreover, we found that the administration of a miR-96-5p inhibitor increased autophagy activation in the mouse hippocampus. 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.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 96 (0), 1-B-P-037-, 2022
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390576037462126592
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed