Mechanisms of neurodegenerative disorders caused by defects in organelle communication

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03255
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: オルガネラ / 脳 / 脂質

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.

Free Research Field

細胞生物学・神経科学

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。