Review Article | Published:

Pericytes of the neurovascular unit: key functions and signaling pathways

Nature Neuroscience volume 19, pages 771783 (2016) | Download Citation

Abstract

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles and post-capillary venules. CNS pericytes are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. They integrate, coordinate and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease, including regulation of the blood–brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation and stem cell activity. Here we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes and neurons that control neurovascular functions. We also review the role of pericytes in CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies.

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Acknowledgements

B.V.Z. is supported by the National Institutes of Health grants R01AG023084, R01NS090904, R01NS034467 and R01AG039452 and the Cure for Alzheimer's Fund.

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Affiliations

  1. Department of Physiology and Biophysics, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

    • Melanie D Sweeney
    •  & Berislav V Zlokovic
  2. Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

    • Melanie D Sweeney
    •  & Berislav V Zlokovic
  3. Systems Biology Group, CytoSolve Research Division, Cambridge, Massachusetts, USA.

    • Shiva Ayyadurai

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Competing interests

S.A. is employed by CytoSolve, Inc. which developed a software-based computational platform for scalable integration of molecular models to offer a systems biology approach to pathway analysis.

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DOI

https://doi.org/10.1038/nn.4288

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