Elucidation of the role of lysoglycolipids on cell death in sphingolipidosis and establishment of therapeutic strategies.

2020 Fiscal Year Final Research Report

• 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
• Keywords: 糖脂質 / リソソーム / オートファジー

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.

Free Research Field

病態生化学

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。