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Sortilin regulates blood-brain barrier integrity.

Andrea E Toth1,2, Hans C Helms2,3, Andras Harazin1

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|October 9, 2021
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Sortilin is a key protein regulating blood-brain barrier (BBB) tightness. Its absence in rats causes BBB leakage and compromised brain endothelial cell junctions, impacting brain homeostasis.

Keywords:
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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • The blood-brain barrier (BBB) is crucial for maintaining brain homeostasis.
  • Factors regulating BBB integrity are not fully understood.
  • Sortilin is a multifunctional receptor with potential roles in cellular regulation.

Purpose of the Study:

  • To investigate the expression and function of sortilin in blood-brain barrier (BBB) cells.
  • To determine sortilin's role in modulating BBB integrity.
  • To elucidate the molecular mechanisms underlying sortilin's effect on BBB function.

Main Methods:

  • Characterization of sortilin expression in vivo and in vitro.
  • Analysis of BBB integrity in sortilin-deficient rats.
  • Assessment of junctional protein localization (zonula occludens-1, VE-cadherin, β-catenin).
  • Evaluation of Akt and ERK1/2 signaling pathways.

Main Results:

  • Sortilin acts as a regulatory protein for BBB tightness.
  • Rats lacking sortilin exhibited a leaky BBB.
  • Absence of sortilin led to altered localization of key junctional proteins.
  • Sortilin deficiency decreased Akt phosphorylation and increased phospho-ERK1/2 levels.
  • Disintegration of brain endothelial cell junctions was observed, compromising BBB integrity.

Conclusions:

  • Sortilin plays a critical role in maintaining blood-brain barrier integrity.
  • Dysregulation of sortilin impacts BBB tightness through modulation of signaling pathways like Akt and MAPK/ERK.
  • Understanding sortilin's function offers insights into healthy and diseased BBB states.