Elucidation of intracellular mechanisms underlying neuronal maturation promoted by solute carrier OCTN1 and biomarker exploration in neuropsychiatric disorders
| Project/Area Number |
16K08266
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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 |
Pharmacology in pharmacy
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| Research Institution | Takasaki University of Health and Welfare (2018)
Kanazawa University (2016-2017) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脳・神経 / 脳神経疾患 / 神経科学 / 薬理学 / 輸送担体 |
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| Outline of Final Research Achievements |
To clarify the pharmacotherapeutic role of the carnitine/organic cation transporter OCTN1, we examined intracellular mechanisms underlying neuronal differentiation and maturation promoted by OCTN1 and whether the in vivo substrate of OCTN1, ergothioneine (ERGO), is available as a biomarker for depression. OCTN1-mediated ERGO uptake promoted neuronal differentiation and maturation through the induction of neurotrophic factors and the activation of mechanistic target of rapamycin (mTOR) and tropomyosin receptor kinase B (TrkB) signaling. There was a positive correlation between the severity of depressive symptoms and ERGO concentration in the blood, suggesting that ERGO could be used as a biomarker for stress-induced neuropsychiatric disorders including depression.
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| Academic Significance and Societal Importance of the Research Achievements |
ERGOによる神経分化および神経成熟促進の細胞内メカニズムが解明されたことにより、水溶性化合物の経口摂取により神経細胞内シグナルを活性化できることが示された。ERGOをシード化合物とする精神・神経疾患の新規治療薬開発への発展が期待される。また、ERGOがストレス性精神・神経疾患のバイオマーカーとなる可能性が示され、今後さらに研究が進むことにより早期診断への応用が期待される。今回の研究をモデルケースとして、他の疾患のバイオマーカー探索にも応用できる。
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] Localizatoin of xenobiotic transporter OCTN1/SLC22A4 in hepatic stellate cells and its protective role in liver fibrosis.2016
Author(s)
Tang Y, Masuo Y, Sakai Y, Wakayama T, Sugiura T, Harada R, Futatsugi A, Komura T, Nakamichi N, Sekiguchi H, Sutoh K, Usumi K, Iseki S, Kaneko S, Kato Y.
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Journal Title
J Pharm Sci
Volume: 印刷中
Issue: 5
Pages: 1779-89
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A mutation in SLC22A4 encoding an organic cation transporter expressed in the cochlea strial endothelium causes human recessive non-syndromic hearing loss DFNB60.2016
Author(s)
Ben Said M, Grati M, Ishimoto T, Zou B, Chakchouk I, Ma Q, Yao Q, Hammami B, Yan D, Mittal R, Nakamichi N, Ghorbel A, Neng L, Tekin M, Shi XR, Kato Y, Masmoudi S, Lu Z, Hmani M, Liu X.
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Journal Title
Human Genetics
Volume: 135(5)
Issue: 5
Pages: 513-524
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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