Development of new therapeutics for kidney diseases by mitochondria homing drug
| Project/Area Number |
18K08199
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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 53040:Nephrology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Suzuki Takehiro 東北大学, 医工学研究科, 特任准教授 (50396438)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ミトコンドリア / ミトフィリン / 酸化ストレス / ミトコンドリア病 / 急性腎障害 / 慢性腎臓病 / 造影剤腎症 / 高血圧 / ATP / 腎臓 |
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| Outline of Final Research Achievements |
Mitochondrial dysfunction causes various mitochondrial diseases, kidney injuries and cardiomyopathy. Intracellular ATP depletion and the increasing mitochondria-derived reactive oxygen species (mitROS) are considered as major pathophysiologic mechanisms of disease progression in mitochondrial abnormalities. Recently we reported mitochondria homing drug, mitochonic acid-5 (MA-5) increased intracellular ATP, decreased mitochondrial ROS and improved cell survivals of fibroblasts from mitochondrial disease patients by binding mitochondrial protein Mitofilin and promoting oligomelization of ATP synthases .MA-5 improved mitochondrial respiratory function in kidney and heart of mitochondrial disease model mice (mitomice).MA-5 also improved the renal function and tubular cell injuries in murine renal ischemia reperfusion,cisplatin induced nephropathy and contrast medium induced nephropathy models.
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| Academic Significance and Societal Importance of the Research Achievements |
ATP産生と同時に酸化ストレスを発生するミトコンドリアの異常は難治性疾患のミトコンドリア病だけでなく、大量のエネルギーを必要とする臓器の難治性疾患であるであるパーキンソン病、筋萎縮性側索硬化症、心不全・心筋症、慢性腎臓病・急性腎障害の原因ともなる。申請者らが開発した新規ミトコンドリア病治療薬MA-5はミトコンドリア病患者細胞の生存率を改善し、細胞内ATPを増加しながも、酸化ストレスは減少させ、ミトコンドリア病モデルマウスの心臓と腎臓のミトコンドリア機能を改善して寿命を延長し、マウスの虚血、抗癌剤、造影剤による急性腎障害を改善するため、より広い難治性疾患の治療薬となる可能性がある。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage.2020
Author(s)
Mishima E, Ishijo M, Kawabe T, Kikuchi K, Akiyama Y, Toyohara T, Suzuki C, Asao A, Ishii N, Fukuda S, Abe T
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Journal Title
Toxins
Volume: 12
Issue: 9
Pages: 547-547
DOI
Related Report
Peer Reviewed / Open Access
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