Abstract
The mammalian neurovascular unit (NVU) is comprised of neurons, glia, and vascular cells. The NVU is the nexus between the cardiovascular and central nervous system (CNS). The central component of the NVU is the blood-brain barrier (BBB) which consists of a monolayer of tightly connected endothelial cells covered by pericytes and further surrounded by astrocytic endfeet. In addition to preventing the diffusion of toxic species into the CNS, the BBB endothelium serves as a dynamic regulatory system facilitating the transport of molecules from the bloodstream to the brain and vis versa. The structural integrity and transport functions of the BBB are maintained, in part, by an orchestra of membrane receptors and transporters including members of the superfamily of G protein-coupled receptors (GPCRs). Here, we provide an overview of GPCRs known to regulate mammalian BBB structure and function and discuss how dysregulation of these pathways plays a role in various neurodegenerative diseases.
Highlights
The brain is the most complex mammalian organ
Daneman et al (2009) determined that Wnt7a and Wnt7b ligands are responsible for angiogenesis in the human cells, they showed that Sonic hedgehog (SHH) released from astrocytes binds to PTCH-1 on the blood-brain barrier (BBB) endothelium and activates SMO causing increased expression of occludin, JAM-1, and VE-cadherin (Alvarez et al, 2011)
We provide—to the best of our knowledge—the first review summarizing the role of G protein-coupled receptors (GPCRs) signaling in regulating mammalian BBB maintenance and development in both healthy and diseased states
Summary
Reviewed by: Ethan Winkler, University of California, San Francisco, United States Alla B. The mammalian neurovascular unit (NVU) is comprised of neurons, glia, and vascular cells. The NVU is the nexus between the cardiovascular and central nervous system (CNS). The central component of the NVU is the blood-brain barrier (BBB) which consists of a monolayer of tightly connected endothelial cells covered by pericytes and further surrounded by astrocytic endfeet. The structural integrity and transport functions of the BBB are maintained, in part, by an orchestra of membrane receptors and transporters including members of the superfamily of G protein-coupled receptors (GPCRs). We provide an overview of GPCRs known to regulate mammalian BBB structure and function and discuss how dysregulation of these pathways plays a role in various neurodegenerative diseases
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