Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood-Brain Barrier In Vitro System

Int J Mol Sci. 2022 Oct 12;23(20):12126. doi: 10.3390/ijms232012126.

Abstract

The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood-brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.

Keywords: LC-MS; PrP 106-126; blood–brain barrier; brain endothelial cells; cytoskeleton.

MeSH terms

  • Blood-Brain Barrier / metabolism
  • Cytoskeleton / metabolism
  • Endothelial Cells / metabolism
  • Endothelium / metabolism
  • Monomeric GTP-Binding Proteins* / metabolism
  • Nitric Oxide / metabolism
  • Peptides / metabolism
  • Peptides / pharmacology
  • Prion Proteins / metabolism
  • Prions* / metabolism
  • Proteomics

Substances

  • Prions
  • Prion Proteins
  • Nitric Oxide
  • Monomeric GTP-Binding Proteins
  • Peptides

Grants and funding

This work was supported by a research grant from Irwin Green Alzheimer’s Research Fund and by a grant to MS and VIT from the Weizmann-Negri Fund and by ISF grant No. 2171/22 and by the United States—Israel Binational Science Foundation (BSF) grant No. 2021205 for IC.