The potential of Slit2 as a therapeutic target for central nervous system disorders

Abstract

Introduction: Slit2 is an extracellular matrix protein that regulates migration of developing axons during central nervous system (CNS) development. Roundabout (Robo) receptors expressed by various cell types in the CNS, mediate intracellular signal transduction pathways for Slit2. Recent studies indicate that Slit2 plays important protective roles in a myriad of processes such as cell migration, immune response, vascular permeability, and angiogenesis in CNS pathologies. Areas covered: This review provides an overview of the diverse functions of Slit2 in CNS disorders and discusses the potential of Slit2 as a therapeutic target. We reviewed preclinical studies reporting the role of Slit2 in various CNS disease models, transgenic animal research, and rodent models that utilized Slit2 as a therapy. Expert opinion: Slit2 exerts a wide array of beneficial effects ranging from anti-migration, blood–brain barrier (BBB) protection, inhibition of peripheral immune cell infiltration, and anti-apoptosis in various disease models. However, a dual role of Slit2 in endothelial permeability has been observed in transgenic animals. Further research on Slit2 will be crucial including key issues such as effects of transgenic overexpression versus exogenous Slit2, function of Slit2 dependent on cellular expression of Robo receptors and the underlying pathology for potential clinical translation.