Research on novel therapy for damaged nerves targeting the mechanism of autophagy interruption by sugar chains
Project/Area Number |
18K15363
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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Research Institution | Nagoya University |
Principal Investigator |
Tomoya Ozaki 名古屋大学, 医学系研究科, 特任助教 (40710588)
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Project Period (FY) |
2018-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 軸索損傷 / dystrophic endball / コンドロイチン硫酸 / オートファジー中断 / cortactin / 神経損傷 / コンドロイチン硫酸プロテオグリカン / オートファジー / コータクチン / 軸索再生 / 糖鎖 |
Outline of Final Research Achievements |
This study demonstrates the existence and function of an intracellular pathway, CS/PTPRσ-cortactin-autophagy interruption, which is part of the formation mechanism of the pathology of damaged neuronal axons, in the dystrophic endball. When dystrophic endballs were cultured and analyzed, we have observed that (i) phosphorylation of cortactin was inhibited in dystrophic endballs. And, we have seen that (ii) knockdown of cortactin gene triggered dystrophic endball phenotypes in growth cone.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、dystrophic endball形成を担うCS/PTPRσ-cortactin-autophagy中断という細胞内経路の存在と機能を実証した。本研究は、100年近く前にCajalが残した謎を解き明かし、神経科学分野、糖鎖研究および受容体型phasphataseの研究分野にインパクト与えた。また本研究が見出した、損傷神経の軸索末端部でのCS/PTPRσ-cortactin-autophagy中断という細胞内イベントは、脊髄損傷など神経損傷に対する新規の治療点を提案するものである。今後は新たに見出せた治療点候補について、理解を深め、動物実験での評価に移っていく予定である。
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis2019
Author(s)
Kazuma Sakamoto, Tomoya Ozaki, Yen-Chun Ko, Cheng-Fang Tsai, Yuanhao Gong, Masayoshi Morozumi, Yoshimoto Ishikawa, Kenji Uchimura, Satomi Nadanaka, Hiroshi Kitagawa, Medel Manuel L. Zulueta, Anandaraju Bandaru, Jun-ichi Tamura, Shang-Cheng Hung, and Kenji Kadomatsu
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Journal Title
Nat. Chem. Biol.
Volume: 15
Issue: 7
Pages: 699-699
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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