2021 Fiscal Year Final Research Report
Elucidation of the pathological role of vacuolar ATPase in lysosomal storage diseases
Project/Area Number |
19K16546
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Osaka Medical and Pharmaceutical University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | ライソゾーム病 / 液胞型プロトンATPase / ファブリー病 / iPS細胞 |
Outline of Final Research Achievements |
In iPS cell-derived cardiomyocytes mimicking Fabry disease, a type of lysosomal storage diseases, the acidification capacity of lysosomes was decreased. This phenomenon led us to focus on a molecule called vacuolar ATPase (V-ATPase), which is a proton pump localized in the lysosomal membrane. Inhibition of V-ATPase function resulted in impaired cardiac function and decreased activity of cathepsin, an acidic protease. Since this study aims to develop a comprehensive treatment for lysosomal storage diseases, we have searched for compounds that activate these molecules and obtained several candidate compounds so far.
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Free Research Field |
難病創薬
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Academic Significance and Societal Importance of the Research Achievements |
ライソゾーム病は, 国の特定疾患に指定されており, 現時点で主な治療法は, それぞれの原因遺伝子に対応した酵素を外から補充する治療 (酵素補充療法) となっている. しかし, 酵素補充療法は治療が継続的であり, なお且つ薬剤が高額なため, 患者の経済的負担が大きく, さらに約60種類にも及ぶライソゾーム病の中で, 各疾患に特異的に対応した酵素を補充する対症療法という位置づけにある. このような現状を受け, 本研究では, ライソゾーム病を根本的に治療する可能性を秘めた包括的制御分子として, V-ATPase, カテプシンに焦点を当て, そこを標的とした安価で効果的な治療法開発の足掛かりを築いた.
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