Mechanisms of neurodegenerative disorders caused by defects in organelle communication
Project/Area Number |
20H03255
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 44010:Cell biology-related
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Research Institution | Nagoya City University |
Principal Investigator |
Shirane Michiko 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (90398082)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
|
Keywords | オルガネラ / 脳 / 脂質 |
Outline of Research at the Start |
皮質脊髄路は巧緻運動を担い、少なくとも霊長類では最も重要な神経回路であるが、軸索変性症HSPはその回路に異常を来す代表的な疾患である。近年軸索変性症HSPとオルガネラ間コミュニケーション(MCSs)の関連が示唆されているが詳細な機構は不明なため、本研究でその解明を目指す。 本研究はわれわれが長年独自に展開してきたプロトルーディン複合体研究に基づいており、MCSs研究との融合により、新たな神経細胞の恒常性維持機構の解明に繋がると期待される。
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Outline of Final Research Achievements |
In this study, we revealed novel functions of intracellular organelle membrane contact sites (MCSs), such as endosome maturation and lipophagy. In addition, we generated mice deficient in the gene for PDZD8 and found abnormal accumulation of cholesterol esters in the brain by lipidome analysis, which was attributed to defective lipophagy mediated by lipid transport. In addition, we found that PDZD8 deficient mice showed abnormal cognitive and emotional behaviors by behavioral battery analysis. The mutations in human PDZD8 gene are known to be associated with brain dysfunction including intellectual disability. Therefore, PDZD8 plays a role in suppression of abnormal accumulation of lipids in the brain by promoting lipophagy, thus contributes to brain function.
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Academic Significance and Societal Importance of the Research Achievements |
近年アルツハイマー病やパーキンソン病などの神経変性疾患において脳内の脂質異常の関与が示唆されており、PDZD8複合体はそれらの機構解明のカギとなることが期待される。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] PDZD8-deficient mice accumulate cholesteryl esters in the brain as a result of impaired lipophagy.2022
Author(s)
Morita K#, Wada M#, Nakatani K, Matsumoto Y, Hayashi N, Yamahata I, Mitsunari K, Mukae N, Takahashi M, Izumi Y, Bamba T, Shirane M*.
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Journal Title
iScience
Volume: 25(12)
Issue: 12
Pages: 105612-105612
DOI
Related Report
Peer Reviewed / Open Access
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[Book] 論文図表を読む作法2022
Author(s)
牛島 俊和、中山 敬一
Total Pages
288
Publisher
羊土社
ISBN
9784758122603
Related Report