Development of medical technology for neuronal regeneration by using LOTUS protein
| Project/Area Number |
17H03561
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Yokohama City University |
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Principal Investigator |
Takei Kohtaro 横浜市立大学, 生命医科学研究科, 教授 (40202163)
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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 |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
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| Keywords | 神経再生 / LOTUS / 神経損傷 / 脳疾患 / Nogo受容体 / タンパク質製剤 / 遺伝子治療 / 再生医療技術 / 脊髄損傷 / 視神経障害 / タンパク質投与 / 脊髄損傷モデル / 視神経障害モデル / 精製タンパク質 / 遺伝子導入 / 高親和性変異体 / 視神経損傷 |
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| Outline of Final Research Achievements |
Brain injury, such as spinal cord injury (SCI), results in severe sensory and motor deficits due to the poor regenerative capacity of the adult central nervous system (CNS) primarily caused by a damaged CNS environment containing a large amount of axonal growth inhibitors, such as Nogo receptor-1 (NgR1), which inhibits axonal regrowth strongly after SCI, and its five ligands. Lateral olfactory tract usher substance (LOTUS) antagonizes NgR1 function, thereby promoting neuronal regeneration and functional recovery after SCI. In this study, we examined whether administration of purified LOTUS protein or lotus gene transfection can be useful for the clinical treatment of SCI and/or optic nerve injury. We found administration of both purified LOTUS protein and lotus gene transfection by AAV vector showed a significant effect on regeneration of injured axons and functional recovery. Thus, the data show the probability of clinical application of LOTUS for future therapy of brain injury.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、外来性に投与したLOTUSタンパク質またはLOTUS遺伝子導入は神経障害において有意な神経再生を惹起して機能改善に寄与することが判明したことから、未だに治療法が確立していない種々の神経障害や様々な脳疾患における軸索変性に対し、LOTUSのタンパク質製剤や遺伝子導入による治療法が奏功する可能性が示唆される。LOTUSは内在性のタンパク質であり成体の中枢神経系に豊富の発現しているが、損傷や疾患によって急激にその発現量が減少するため、LOTUSの機能不全によって神経再生が困難になると考えられる。従って、LOTUSを外来性に補填する補充療法は理に適った新たな治療法として期待される。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Axonal regeneration and functional recovery driven by endogeneous Nogo receptor antagonist LOTUS in a rat model of unilateral pyramidotomy.2020
Author(s)
Ueno, R., Takase, H., Suenaga, J., Kishimoto, M., Kurihara, Y., Takei, K., Kawahara, N., and Yamamoto
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Journal Title
Experimental Neurology
Volume: 323
Pages: 113068-113068
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LOUTS inhibits neuronal apoptosis and promotes tract regeneration in contusive spinal cord injury model mice.2018
Author(s)
Ito, S., Nagoshi, N., Tsuji, O., Shibata, S., Shinozaki, M., Kawabata, S., Kojima, K., Yasitake, K., Hirokawa, T., Matsumoto, M., Takei, K., Nakamura, M., and Okano, H.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] The soluble form of LOTUS inhibits Nogo receptor-mediated signaling by interfering with the interaction between Nogo receptor type 1 and p75 neurotrophn receptor2018
Author(s)
Kawakami, Y., Kurihara, Y., Saito, Y., Fujita, Y., Yamashita, T., and Takei, K.
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Journal Title
Journal of Neuroscience
Volume: 38
Pages: 2589-2604
Related Report
Peer Reviewed
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[Journal Article] Regulation of axonal regeneration by the level of function of endogenous Nogo receptor antagonist LOTUS2017
Author(s)
Hirokawa, T., Zou, Y., Kurihara, Y., Jiang, Z., Sakakibara, Y., Ito, H., Funakoshi, K., Kawahara, N., Goshima, Y., Strittmatter, S.M., and Takei, K.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 12119-12119
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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