SERONE E.1,3, PORCU G.1, DI GIANDOMENICO D.1, DE NARDIS V.1, SCARDAPANE M.4, POMA A.M.2 RAGNINI-WILSON A.1,2
Depts. of Cellular and Translational Pharmacology1 and Clinical Pharmacology and Epidemiology4 - Fondazione Mario Negri Sud, S.M. Imbaro, Italy; Dept. of Biology, University of Rome Tor Vergata, Italy2 ; Dept. of Life, Health and Environmental Sciences, University of L’Aquila, Italy3
ABSTRACT: One of the crucial points in screening compounds acting in re-myelination processes is the identification of the appropriate cell-based assay. Insufficient re-myelination in chronic Relapsing Remitting Multiple Sclerosis (RRMS) patients is thought to be linked to the inability of post-mitotic Oligodendrocyte Precursor Cells (OPCs) that have migrated to lesions to express myelin genes. The major limitation in the use of primary OPCs in high-throughput microscopy-based screenings to identify pro-myelinating drugs is the OPC isolation and propagation technologies. An immortalized oligodendrocyte precursos cell line, named Oli-neu, has been previously developed and well characterized for myelin gene expression up to the process of axon wrapping (Jung et al., 1995; White and Krämers-Albers 2014). Here we report a further improvement of this cell line for the purpose of image-based automated drug library screening aiming to identify drugs acting in re-myelination processes. Oli-neuM was obtained by genetically engineering the Oli-neu cell line and it was then used to screen the Prestwick Chemical Library® of 1,200 Food and Drug Administration (FDA)-approved small molecules for their ability to up-regulate Myelin Basic Protein (MBP) expression using an HT/HCA microscopy ScanR platform (Olympus). The use of Oli-neuM in HTM-HCA-based screens allowed the selection of drugs targeting well-defined pathways leading to myelination as well as the selection of potential pro-myelinating agents.