| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Outline of Final Research Achievements |
Pelizaeus-Merzbacher disease (PMD) is caused by point mutations or copy number changes in the proteolipid protein 1 gene (PLP1). Amino acid-substituted PLP1 protein is unable to fold properly and is subsequently degraded and/or restrictedly translated, resulting in a decrease in the PLP1 protein level and a failure to localize to the membrane. Furthermore, misfolded proteins increase the burden on the intracellular quality control system and trafficking, finally resulting in cell apoptosis. We established a cell line stably expressing PLP1A243V fused with green fluorescent protein in oligodendrocyte-derived MO3.13 cells. We screened a chemical library that increased both the total intensity of PLP1-A243V in the whole cell and the cell membrane localization. We analyzed the change in the endoplasmic reticulum stress and the gene expression of candidate chemicals. Piracetam significantly increased the PLP1A243Vintensity and membrane localization and decreased the ER stress.
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