2022 Fiscal Year Final Research Report
Creation of Novel Therapeutics Targeting Astrocytes in Sandhoff's Disease
| Project/Area Number |
19K06914
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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 46010:Neuroscience-general-related
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | ザンドホッフ病 / 活性化アストロサイト / 脳炎症 / リソソーム病 |
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| Outline of Final Research Achievements |
In this study, Sandhoff disease model mice were investigated as an animal model of encephalitis. In addition, inflammatory cytokines (IL-1α and TNFα) were added to cultured astrocytes to analyze expression of various proteins and drug screening.
When cultured astrocytes were stimulated by inflammatory cytokines, we identified novel proteins that were altered in addition to marker proteins expressed in activated astrocytes. The changes were similar in a mouse model of Sandhoff's disease. Next, to analyze the regulation of astrocyte activation by inflammatory cytokines, I screened for drugs using the increase or decrease of NF-kB signal as an indicator. As a result, various candidate molecules were obtained.
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| Free Research Field |
神経薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
脳炎症において、アストロサイトの活性化を含むグリオーシスは、新規の治療標的になりうることが示されてきた。本研究で標的としているザンドホッフ病は希少疾患であり、ヒトでの研究成果は極めて乏しい。そのため、ヒトでの疾患を良く反映し脳全体にグリオーシスを示すザンドホッフ病モデルマウスや、培養アストロサイトを利用し解析した。本研究成果において、活性化アストロサイトで増加する新規のタンパク質を同定し、さらにグリアを作用標的とした候補分子を得たことは、脳炎症を伴う神経系疾患の治療標的創出の一助となりうる。
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