title: Evidence against a role of P-glycoprotein in the clearance of the Alzheimer's disease Aβ1-42 peptides.
abstract: It has been proposed that the amyloid-β peptides (Aβ) cause the neuronal degeneration in the Alzheimer's disease brain. An imbalance between peptide production at the neuronal level and their elimination across the blood-brain-barrier (BBB) results in peptide accumulation inside the brain. The identification and functional characterization of the transport systems in the BBB with the capacity to transport Aβ is crucial for the understanding of Aβ peptide traffic from the brain to the blood. In this context, it has been suggested that the P-glycoprotein (P-gp), expressed in endothelial cells of the BBB, plays a role in the elimination of Aβ. However, there is little, if any, experimental evidence to support this; therefore, the aim of this investigation was to determine whether P-gp is capable of transporting Aβ peptides. Our results show that ATPase activity measured in plasma membrane vesicles of K562 cells overexpressing P-gp is not increased by the presence of Aβ42, suggesting that Aβ42 is not a P-gp substrate. Similarly, P-gp of pirarubicin was unaffected by Aβ42. Moreover, the overexpression of P-gp does not protect cells against Aβ42 toxicity. Taken together, our results support the conclusion that Aβ42 is not transported by P-gp.
authors.affiliation: Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), UFR-SMBH, Université Paris 13, 74 rue Marcel Cachin, 93017, Bobigny, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bello
authors.forename: Milena
authors.initials: M
authors.lastname: Salerno
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D021381:Protein Transport
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)