Elucidation of the role of lysoglycolipids on cell death in sphingolipidosis and establishment of therapeutic strategies.
| Project/Area Number |
18K06658
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
TSUJI Daisuke 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (00423400)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| 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)
|
|---|
| 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 |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(48 results)
-
[Journal Article] Development of a 1,3a,6a-Triazapentalene Derivative as a Compact and Thiol-specific Fluorescent Labeling Reagent2020
Author(s)
Atsushi Nakayama, Akira Otani, Tsubasa Inokuma, Daisuke Tsuji, Haruka Mukaiyama, Akira Nakayama, Kohji Itoh, Akira Otaka, Keiji Tanino, and Kosuke Namba
-
Journal Title
Communications Chemistry
Volume: 3
Issue: 1
Pages: 1-9
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Linaburiosides A-D, acylated iridoid glucosides from Linaria buriatica.2020
Author(s)
Niwa K, Yi R, Tanaka N, Kitaguchi S, Tsuji D, Kim SY, Tsogtbaatar A, Bunddulam P, Kawazoe K, Kojoma M, Damdinjav D, Itoh K, Kashiwada Y
-
Journal Title
Phytochemistry
Volume: 171
Pages: 112247-112247
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Molecular pathogenesis and innovative therapy for lysosomal neuraminidase 1 (neu1)deficiencies(sialidosis and galactosialidoisi).2019
Author(s)
Kohji Itoh, Jun Tsukimoto, Daisuke Tsuji, Yuto Horii, Toshiki Iniwa, Yuri Fukushi, Haruna Andoh, Simona P, Cabitta L, Grassi S, Prinetti A and Sonnino S
Organizer
Glyco25 イタリア・ミラノ
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
[Presentation] 組換えカイコ絹糸腺で高発現するヒトリソソーム酵素のN型糖鎖改変と医薬応用2019
Author(s)
伊藤 孝司, 西岡 宗一郎, 篠田 知果, 竹内 美絵, 福士 友理, 月本 準, 辻 大輔, 小林 功, 炭谷 めぐみ, 飯塚 哲也, 木下 嵩司, 三谷 藍, 堂崎 雅仁, 須田 稔, 松崎 祐二, 飯野 健太, 瀬筒 秀樹
Organizer
第38回 日本糖質学会年会
Related Report
-
-
-
[Presentation] イネ科植物の鉄イオン取り込み機構の解明に向けた化学プローブの開発2019
Author(s)
船曵 早希, 佐々木 彩花, 向山 はるか, 村田 佳子, 辻 大輔, カランジット サンギータ, 中山 淳, 難波 康祐, 占部 敦美, 辻 大輔, 伊藤 孝司
Organizer
第14回トランスポーター研究会年会
Related Report
-
[Presentation] 天然マクロライドの全合成が拓く新規多発性骨髄腫治療薬2019
Author(s)
浜田 麻衣, 森崎 巧也, 中山 淳, 寺町 順平, 辻 大輔, 重永 章, 山本 武範, 篠原 康雄, 大髙 章, 伊藤 孝司, 安部 正博, 難波 康祐
Organizer
創薬懇話会2019 in 秋保(仙台)
Related Report
-
-
-
-
-
-
-
-
-
