2020 Fiscal Year Final Research Report
Identification of causative genes for hereditary spastic paraplegia
| Project/Area Number |
18K07495
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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 52020:Neurology-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高 紀信 山梨大学, 大学院総合研究部, 臨床助教 (00622557)
一瀬 佑太 山梨大学, 大学院総合研究部, 臨床助教 (90644782)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 遺伝性痙性対麻痺 / 遺伝子 / 分子病態 / UBAP1 / SPG80 |
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| Outline of Final Research Achievements |
We identified that mutations in the UBAP1 gene cause a new type (SPG80) of hereditary spastic paraplegia (HSP) independently with European and American study groups. The full-length UBAP1 protein is involved in endosomal dynamics in neurons, while loss of UBAP1 function may perturb endosomal fusion and sorting of ubiquitinated cargos.These effects could be more prominent in neurons, thereby giving rise to the phenotype of a neurodegenerative disease such as HSP. We established the UBAP1 knock-in mice to elucidate the further molecular mechanism underlying SPG80 and to find the disease-modifying therapy for SPG80. In addition, we found a lot of novel mutations in SPG4, SPG5, SPG9B, SPG11, SPG57, SPG72, PLA2G6, VCP, and AP-4 associated HSP, and performed clinical and genetic studies of these HSP.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、オールジャパン研究体制であるJapan Spastic Paraplegia Research Consortium (JASPAC) を通して新規原因遺伝子UBAP1 (SPG80) の同定を行うことができた。日本から世界に向けて新しい情報を発信できたことは、学術的意義が大きいと思われる。さらに我々は、UBAP1ノックインマウスの作成を行ったが、本マウスは、今後の薬剤スクリーニングに動物モデルとして使用することができるので、SPG80の疾患修飾療法の開発に大いに役立つことと思われる。
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