Drug connectivity mapping and functional analysis reveals therapeutic small molecules that differentially modulate myelination

AbstractOligodendrocytes are the myelin forming cells of the central nervous system (CNS) and are generated from oligodendrocyte progenitor cells (OPCs). Disruption or loss of oligodendrocytes and myelin has devastating effects on CNS function and integrity, which occurs in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease (AD) and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular r…