| Project/Area Number |
18K07045
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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 49030:Experimental pathology-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAZAKI Tetsuo 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (90330208)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | CLN6 / NCL / ER / 神経セロイドリポフスチン症 / 小胞体 / 凝集体 / 神経性セロイドリポフスチン症 / Kufs病 / クリスタリン |
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| Outline of Final Research Achievements |
This study aims to establish a therapeutic strategy for "aggregate deposition diseases" commonly characterized by the accumulation of protein aggregates. This research was developed based on our previous finding that the endoplasmic reticulum (ER) membrane microenvironment has the ability to prevent protein aggregate formation and that the ER transmembrane protein CLN6, whose function is unknown, is the molecular entity of the ER-driven anti-aggregate activity. We here show that (1) mutations in the CLN6 gene limit CLN6’s anti-aggregate activity, but not in an "all-or-nothing" manner, (2) functional interference between CLN6 mutants can abrogate CLN6’s anti-aggregate activity, and (3) CLN6’s luminal tail would be spatially restricted, ensuring that wild-type CLN6 exert its anti-aggregate activity.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化が急激に進む我が国で、パーキンソン病やアルツハイマー病をはじめとする凝集体難病が社会問題化しているのは周知の事実である。しかもその根治療法の開発が滞っているのが現状である。本研究成果は凝集体難病治療に向けた標的分子とその制御に不可欠なメカニズムを提示したものであり、一連の疾患の「予防」を可能にすることが期待される。また、標的分子として同定したCLN6を原因遺伝子とする遺伝性神経変性難病の発症機構に迫るものでもあり、学術的・社会的意義が極めて高い成果といえる。
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