| Project/Area Number |
18K06658
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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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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TSUJI Daisuke 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (00423400)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 糖脂質 / リソソーム / オートファジー / リソソーム病 / リゾ糖脂質 / シグナル伝達 / スフィンゴリピドーシス / オルガネラ |
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| Outline of Final Research Achievements |
Sphingolipidosis causes severe central nervous system (CNS) symptoms, however, the mechanism of pathogenesis is unknown and no fundamental treatment has been established. Although it is known that lyso-glycosphingolipids (lyso-GSLs), in which the fatty acid portion of glycosphingolipids (GSLs) is truncated, accumulate in sphingolipidosis, their relationship to the pathogenesis is unknown. In the present study, we analyzed the effects of lyso-GSLs on neuronal cell death in sphingolipidosis.
To investigate the cause of neuronal cell death caused by lyso-GSLs, we added them to human neuronal cell models and analyzed their effects. The results showed that llyso-GSLs attenuated PI3K/Akt signaling. Furthermore, we demonstrated that lyso-GSLs directly inhibit the activity of PI3K.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は治療法の存在しない糖脂質蓄積症の病態解析を行い、リゾ糖脂質が神経細胞死に影響を与えていることを明らかにした。またシグナル伝達阻害を起こすことを明らかにしたため、治療薬の開発に役立つと考えられる。この成果は、GM2ガングリオシドーシスだけでなく、他のスフィンゴリピドーシスに応用できる可能性が高い。
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