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2022 Fiscal Year Final Research Report

Establishment of CNS barrier-targeted drug development based on generation of a new field, Barrier Systems Biology

Research Project

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Project/Area Number 20H03399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionTohoku University

Principal Investigator

Uchida Yasuo  東北大学, 薬学研究科, 准教授 (70583590)

Co-Investigator(Kenkyū-buntansha) 三枝 大輔  帝京大学, 薬学部, 准教授 (90545237)
水野 忠快  東京大学, 大学院薬学系研究科(薬学部), 助教 (90736050)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywords中枢関門 / 血液脳関門 / バリアーシステム生物学 / 中枢関門(原因)仮説 / 中枢関門創薬 / SWATH / OLSA
Outline of Final Research Achievements

The establishment of new drug discovery fields is an important issue in making a breakthrough in the sluggish development of new drugs for the treatment of CNS diseases. Although abnormalities in the blood-brain barrier may be a cause of CNS diseases, there are no examples of drug discovery targeting the blood-brain barrier. The present study proves that drug therapies targeting the blood-brain barrier can ameliorate CNS diseases. Using multiple sclerosis as a model for a disease with a pattern of disruption of tight junctions, the Annexin A2 pathway was found to be important in the disruption of the barrier, and the treatment was demonstrated. In a model of Alzheimer's disease as a disease pattern in which the barrier is not disrupted, the protein translation pathway was found to be enhanced in the patient's cerebral vasculature, demonstrating that ribosome inhibition is effective.

Free Research Field

分子システムズ薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究は、「血液脳関門の病態分子機構をシステマティックかつ定量的に捉え、その中から有望な創薬標的を見出し、中枢疾患を治療する」という中枢関門創薬の初めての成功例であるとともに、関門機能をシステマティックに研究する新学問「バリアシステム生物学」の開拓につながるものである。
これまでに中枢関門を標的とした創薬は前例がないことや、中枢疾患は数十種類存在することから、今後、この戦略によって、有望な中枢疾患治療薬を創出でき、中枢疾患の新たな創薬フィールドを創出できると期待される。

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Published: 2024-01-30  

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