pathophysiological analysis of a mouse model of cerebral leukoencephalopathy and search for pathogenesis-related metabolites

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860371
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kyushu University
• Principal Investigator: yagi mikako 九州大学, ARO次世代医療センター, 学術研究員 (70536135)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ミトコンドリア / p32/C1qbp / 白質脳症

Outline of Final Research Achievements

Mitochondrial dysfunction represents a critical step during the pathogenesis of neurodegenerative disease. The p32/C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, how p32 lead to neurodegeneration remains unclear. Neural-specific p32 deletion resulted in white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions, similar to mitochondrial leukoencephalopathy. Metabolomics analysis showed increased glycolysis, decreased GABA signaling, lipid synthesis and impaired amino acid metabolism in p32cKO tissue. Mitochondrial function in oligodendrocytes and neurons is therefore essential for myelination and axonal maintenance, suggesting that mitochondrial dysfunction contributes to leukoencephalopathy.

Free Research Field

分子生物学