Molecular mechanisms underlying differentiation and developmental abnormalities of the nervous system that occurs during the asymptomatic phase of Sandhoff's disease and application to drug discovery

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: Oishi Kazuhiko 明治薬科大学, 薬学部, 教授 (80203701)
• Co-Investigator(Kenkyū-buntansha): 小川 泰弘 明治薬科大学, 薬学部, 講師 (00531948)
• Research Collaborator: Sakuraba Hitoshi ; Togawa Tadayasu ; Kanekura Takuro ; Kaizu Katsutoshi ; Irisa Masahiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: リソソーム病 / 神経分化 / iPS細胞

Outline of Final Research Achievements

Sandhoff's disease (SD) is a disease caused by a deficiency or abnormality of lysosomal hydrolytic enzymes. This deficiency causes aberrant lysosomal accumulation of GM2 gangliosides mainly in neuronal cells. We clarified that differentiation and developmental abnormalities of the nervous system occur early before the appearance of symptoms of SD, using a mouse model of SD and SD-iPS cells. By drug discovery screening system using SD-iPS cells, we found a new low molecular compound that can improve differentiation and developmental abnormality of nervous system.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、「SDの発症前早期に潜在する脳神経系分化発達シグナリングの破綻が神経系の分化・発達異常の原因となり、神経変性が進行し脳神経系の機能が障害され発症する。」という新たな説を導くことができた。また、本研究で得られた成果をヒトの系へ帰納することで、病態の本質的解明が初めて可能となる。SDの病態の本質的解明に繋がるばかりでなく、SDの新たな治療戦略の開発基盤を提供できると考えられ、その効果は絶大である。