title: Transport of a Prolyl Endopeptidase Inhibitory Peptide across the Blood-Brain Barrier Demonstrated Using the hCMEC/D3 Cell Line Transcytosis Assay.
abstract: The blood-brain barrier (BBB) remains a significant hurdle for treatment of central nervous system (CNS) and mental health disorders. A prolyl endopeptidase (PEP) inhibitory peptide with the amino acid sequence proline-proline-leucine (PPL) was chemically synthesized labeled with 5-FAM and assessed using a transcytosis assay for its ability to cross the BBB. Transport of this peptide across the BBB was determined using an in vitro model of the human BBB, which utilizes the human cerebral microvascular endothelial cell line (hCMEC/D3). Uptake and transport of 5-FAM-PPL across the hCMEC/D3 cell model was determined using confocal microscopy and mass spectrometry. This is an important parameter in determining whether peptides may reach the target organ (i.e., the brain and central nervous system).This work assessed, for the first time, the ability of a food-derived PEP inhibitory peptide to cross the BBB without the use of animal models.
authors.affiliation: Food BioSciences Department, Teagasc, The Irish Agricultural and Food Development Authority , Ashtown, Dublin 15, Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Hayes
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU) , 1432 Ås, Oslo area, Norway.
authors.forename: Lars Fredrik
authors.initials: LF
authors.lastname: Moen
authors.affiliation: Food Chemistry and Technology Department, National Food Imaging Centre , Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Mark A E
authors.initials: MA
authors.lastname: Auty
authors.affiliation: Department of Chemistry, Biotechnology and Food Science, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU) , 1432 Ås, Oslo area, Norway.
authors.forename: Tor Erling
authors.initials: TE
authors.lastname: Lea
mesh_terms: D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000378:metabolism; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
keywords: blood−brain barrier; endothelium; hCMEC/D3 cell line; inhibitory peptides; prolyl endopeptidase; transcytosis