Transport of Alzheimer’s associated amyloid-β catalyzed by P-glycoprotein

• DOI: 10.1371/journal.pone.0250371
• Publication Date: 2021-04-26T19:32:20Z
• Authors: James W. McCormick; Lauren A. McCormick; Gang Chen; Pia D. Vogel; John G. Wise
• Keywords: Amyloid (mycology)

P-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and implicated Alzheimer's disease (AD). However, previous studies on ability of P-gp to directly transport associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, substrate accumulation cell culture, biochemical activity assays show that actively transports Aβ. We observed Aβ40 Aβ42 monomers by explicit MD simulations putative catalytic cycle. In vitro with overexpressing cells, enhanced fluorescently labeled presence Tariquidar, potent inhibitor. also showed stimulated ATP hydrolysis isolated nanodiscs. Our findings expand profile P-gp, suggest may contribute onset progression AD.