TY - JOUR
T1 - The potential of Slit2 as a therapeutic target for central nervous system disorders
AU - Sherchan, Prativa
AU - Travis, Zachary D.
AU - Tang, Jiping
AU - Zhang, John H.
N1 - Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/8/2
Y1 - 2020/8/2
N2 - 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.
AB - 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.
KW - Anti-migration
KW - Slit2
KW - apoptosis
KW - blood brain barrier
KW - glioma
KW - ischemic stroke
KW - neuroinflammation
KW - roundabout
KW - surgical brain injury
KW - traumatic brain injury
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U2 - 10.1080/14728222.2020.1766445
DO - 10.1080/14728222.2020.1766445
M3 - Review article
C2 - 32378435
SN - 1472-8222
VL - 24
SP - 805
EP - 818
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 8
ER -