Development of molecular therapy for polyglutamine diseases by reverse structure-based drug design
Project/Area Number |
26713030
|
Research Category |
Grant-in-Aid for Young Scientists (A)
|
Allocation Type | Partial Multi-year Fund |
Research Field |
Neurology
|
Research Institution | Osaka University (2016-2017) Kyoto University (2014-2015) |
Principal Investigator |
|
Project Period (FY) |
2014-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
|
Keywords | ポリグルタミン病 / 分子シャペロン / エクソソーム / 脳内送達 / 凝集阻害化合物 / 脳内移行性キャリア / 血液脳関門 / ドラッグデザイン |
Outline of Final Research Achievements |
Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are brain diseases with no effective therapies established to date. In this study, we aimed to develop therapy for polyglutamine diseases, one of the neurodegenerative diseases, and obtained three results. (1) We performed detailed analysis on the binding mode of disease-associated polyglutamine proteins with the aggregation inhibitor. (2) We found a novel proteostasis machinery that molecular chaperones are secreted from cells and transmitted to the other cells via exosomes, one of the extracellular vesicles, and suppress neurodegeneration in a non-cell autonomous manner.(3) We successfully developed peptide carriers that can pass through the blood-brain barrier, which can be utilized as brain delivery carriers for drugs. These results provide important knowledge for drug development for polyglutamine diseases and neurodegenerative diseases.
|
Report
(5 results)
Research Products
(35 results)