Semaphorin 3s signaling in the central nervous system: Mechanisms and therapeutic implication for brain diseases

Class 3 semaphorins (Sema3s), identified as secreted soluble proteins, present many therapeutic potentials. Recent evidence has suggested that Sema3s as molecular cue participate in neuroregulation, angiogenesis, and microenvironment homeostasis of the central nervous system. Moreover, Sema3s signaling pathways may be targeted for enhancing neural network connectivity, promoting neural regeneration and repair, and inhibiting pathological angiogenesis. Due to the complex co-expression patterns and crosstalk among Sema3s, new drugs targeting Sema3s-related signaling pathways are expected to be discovered to counter brain diseases. This review summarizes the specific roles of Sema3s in pathological processes of various brain diseases, and provides potential targeted strategies for the prevention and treatment.