Phenotypic screening with primary neurons to identify drug targets for regeneration and degeneration

High-throughput, target-based screening techniques have been utilized extensively for drug discovery in the past several decades. However, the need for more predictive in vitro models of in vivo disease states has generated a shift in strategy towards phenotype-based screens. Phenotype based screens are particularly valuable in studying complex conditions such as CNS injury and degenerative disease, as many factors can contribute to a specific cellular response. In this review, we will discuss different screening frameworks and their relative utility in examining mechanisms of neurodegeneration and axon regrowth, particularly in cell-based in vitro disease models.