Search for the therapeutic methods for SLC19A3 deficiency using disease model mice.
| Project/Area Number |
17K10070
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野村 紀子 愛知県医療療育総合センター発達障害研究所, 遺伝子医療研究部, 専門員 (00393132)
山田 憲一郎 愛知県医療療育総合センター発達障害研究所, 遺伝子医療研究部, 主任研究員 (30291173)
千葉 陽一 香川大学, 医学部, 講師 (30372113)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | SLC19A3遺伝子 / チアミン / 疾患モデルマウス / 治療 / ミクログリア / 神経細胞死 / SLC19A3 |
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| Outline of Final Research Achievements |
Deficiency of a thiamine transporter, SLC19A3, is an autosomal recessive disorder and infantile case shows most severe penotype of brain disturbance. Thiamine is effective in patients with SLC19A3 deficiency, but there is an urgent need to identify another effective drug to improve symptoms. In the present study, drugs were administered to homozygous deletion (KO) mice of Slc19a3 gene fed a thiamine-restricted diet, and the pathological findings of the brains were analyzed using an immunohistological method. As a result, in the group treated with minomycin and exendin, the loss of NeuN-positive cells in the thalamus and the increase of GFAP-positive cells and Iba1-positive cells in the thalamus were observed as in the untreated KO mice. However, NAC-treated KO mice had reduced abnormal brain findings. Taken together, NAC can suppress the exacerbation of brain damage due to thiamin restriction in Slc19a3 KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
チアミントランスポーターであるSLC19A3遺伝子の欠損症では、チアミンの摂取量が著しく低下するので、脳の活性型チアミン二リン酸（チアミンピロリン酸：TPP）が不足し、主にミトコンドリアでのエネルギー産生が障害され、リー脳症に類似した脳症状や脳MRI所見が見られる。従って、本研究により、体内で欠乏しているチアミン以外の本欠損症に有効な薬剤を同定することは、本欠損症のみならず、リー脳症の原因となる様々なミトコンドリアに異常が見られる疾患の治療に有効と考えられる。本研究では、NAC(Ｎアセチルシステイン）が本欠損症に有効なことを明らかにした。従って、NACはリー脳症の治療の候補薬である。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS).2017
Author(s)
Suzuki Y, Enokido Y, Yamada K, Inaba M, Kuwata K, Hanada N, Morishita T, Mizuno S, Wakamatsu N.
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Journal Title
Oncotarget
Volume: 8(28)
Issue: 28
Pages: 45470-45483
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular reminiscent of Mowat-Wilson syndrome with Ehlers-Danlos syndrome.2017
Author(s)
Teraishi M, Takaishi M, Nakajima K, Ikeda M, Higashi Y, Shimoda S, Asada Y, Hijikata A, Ohara O, Hirai Y, Mizuno S, Fukada T, Furukawa T, Wakamatsu N, Sano S.
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Journal Title
Scientific Report
Volume: 7:46565
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] phenotypes from infantile lethality to mild learning difficulties2017
Author(s)
Tanigawa J, Mimatsu H, Mizuno S, Okamoto N, Fukushi D, Tominaga K, Kidokoro H, Muramatsu Y, Nishi E, Nakamura S, Motooka D, Nomura N, Hayasaka K, Niihori T, Aoki Y, Nabatame S, Hayakawa M, Natsume J, Ozono K, Kinoshita T, Wakamatsu N, Murakami Y
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Journal Title
Human Mutation
Volume: 印刷中
Issue: 7
Pages: 805-815
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 大脳皮質神経細胞移動におけるSADキナーゼの役割2019
Author(s)
中西圭子, 丹伊田浩行, 田畑秀典, 城村由和, 植田高史, 山田憲一郎, 永田浩一, 若松延昭, 岸 将史, 鵜川眞也, 島田昌一, 東 雄二郎, 中西 真
Organizer
第42回日本神経科学大会/第62回神経化学会大会合同大会（新潟）2019.7.26.
Related Report
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