A novel disease modification strategy for Parkinson disease by PGK enhancement
| Project/Area Number |
18K07506
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KASAI TAKASHI 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70516062)
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| Co-Investigator(Kenkyū-buntansha) |
山口 政光 京都工芸繊維大学, 応用生物学系, 教授 (00182460)
中雄 裕美子 (東裕美子 / 東 裕美子) 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (00453093)
徳田 隆彦 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所・脳機能イメージング研究部, 医長 (80242692)
吉田 英樹 京都工芸繊維大学, 応用生物学系, 准教授 (30570600)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | パーキンソン病 / PGK / Pgk / ショウジョウバエ / 解糖系 |
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| Outline of Final Research Achievements |
Mutations in the gene encoding phhosphoglycerate kinase (PGK) has been found to be susceptibility to PD. PGK is a key enzyme in the glycolytic pathway catalyzing the reaction from 1.3-diphosphoglycerate to 3-phosphoglycerate. Here, we established the PD model targeting of the Drosophila Pgk. DA neuron-specific Pgk knockdown lead to locomotive defect in both young and aged adult flies accompanied with progressive DA neuron loss with ageing. Pgk knockdown in DA neuron decreased dopamine level in central nerves system (CNS) of both young and aged adult flies. These phenotypes are similar to defects observed in human PD patients, suggesting that the established Pgk knockdown flies are a promising model for PD. In addition, pan-neuron-specific Pgk knockdown induced low ATP level and accumulation of reactive oxygen species (ROS) in CNS of third instar larvae. These results indicate that failure of energy production system causes locomotive defects accompanied with neuronal degeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病の治療を目的とした研究の一環として、最近報告された解糖系酵素PGKの欠損家系におけるパーキンソン症状に注目し、PGK遺伝子の発現抑制がどのようにパーキンソン病を引き起こしているのかを解明する研究を遂行しました。
PGK遺伝子機能を抑制したショウジョウバエにおいてドパミン神経減少を含むパーキンソン病に特徴的な変化を確認し、これらの変化がエネルギー産生障害に起因することを裏付ける結果を得ました。こうした結果はパーキンソン病治療においてPGK活性の促進が重要であることを意味しておりPGK活性促進を介した新しいパーキンソン病治療戦略を提案する足掛かりとなる成果です。
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS2019
Author(s)
Takashi Kasai, Yuta Kojima, Takuma Ohmichi, Harutsugu Tatebe, Yukiko Tsuji, Yu-Ichi Noto, Fukiko Kitani-Morii, Makiko Shinomoto, David Allsop,Toshiki Mizuno, Takahiko Tokuda
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Journal Title
Annals of Clinical Translational Neurology
Volume: 6
Issue: 12
Pages: 2489-2502
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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