Drug screening for Pelizaeus-Merzbacher disease by quantifying the total levels and membrane localization of PLP1

The objective of this study was to identify therapeutic chemicals for PMD by quantifying the total levels and membrane localization of PLP1.MethodWe established a cell line stably expressing PLP1A243V fused with green fluorescent protein in oligodendrocyte-derived MO3.13 cells. We screened a chemical library composed of drugs approved for central nervous system disorders that increased both the total intensity of PLP1A243V in the whole cell and the cell membrane localization. We analyzed the change in the endoplasmic reticulum (ER) stress and the gene expression of candidate chemicals using a micro-array analysis. Finally, we tested the in vivo effectiveness using myelin synthesis deficient (msd) mice with PlpA243V.Results and conclusionPiracetam significantly increased the PLP1A243V intensity and membrane localization and decreased the ER stress. It was also shown to reverse the gene expression changes induced by PLP1A243V in a micro-array analysis. However, in vivo treatment of piracetam did not improve the survival of msd mice (Plp1A243V).
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research