2022 Fiscal Year Final Research Report
Pathophysiology and therapeutic development of mitochondrial axonal transport disorders using Drosophila model of neurological diseases
| Project/Area Number |
19K16924
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Kitani-Morii Fukiko 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60806842)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 疾患モデル / 神経変性疾患 / ショウジョウバエ |
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| Outline of Final Research Achievements |
The aim of this study was to identify molecules involved in mitochondrial axonal transport, analyze their functions, and develop therapeutic strategies. Similarly, motor function was improved in an amyotrophic lateral sclerosis model.In Drosophila, a neural-specific human TDP43 transgenic strain, mating with the Klp68D-KD strain also prolonged survival.Comprehensive gene expression analysis showed a significant down-regulation of Hsp70, and oral administration of an Hsp70 inhibitor tended to improve locomotor function in adults, but the difference did not reach statistical significance.
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| Free Research Field |
神経変性疾患
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| Academic Significance and Societal Importance of the Research Achievements |
神経変性疾患においてミトコンドリアの軸索輸送は長い神経の末端までエネルギーを供給するシステムとして重要であるが、その運搬に関与する具体的な分子は不明点が多かった。本研究でショウジョウバエKlp68D（ヒトKif3Bホモログ）は複数の運動神経変性疾患の原因遺伝子と遺伝的相互作用を示し、発現抑制によって予後の改善が得られた。さらにHsp70の関与が示された。複数の異なる遺伝子で共通に変化する分子の同定に至ったことにより幅広い神経変性疾患への応用が可能な治療標的となり得る
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