ChemInform Abstract: Syntheses of Taxuspine C Derivatives as Functional Inhibitors of P-Glycoprotein, an ATP-Associated Cell-Membrane Transporter.

ChemInform ◽  
2010 ◽  
Vol 29 (52) ◽  
pp. no-no
Author(s):  
M. SAKO ◽  
H. SUZUKI ◽  
K. HIROTA
Keyword(s):  
Cell Membrane ◽  
Membrane Transporter ◽  
P Glycoprotein

P-Glycoprotein Contributes to Cell Membrane Depolarization of Hippocampus and Neocortex in a Model of Repetitive Seizures Induced by Pentylenetetrazole in Rats

2013 ◽  
Vol 19 (38) ◽  
pp. 6732-6738 ◽  
Author(s):  
Jerónimo A. Auzmendi ◽  
Sandra Orozco-Suárez ◽  
Ivette Bañuelos-Cabrera ◽  
María Eva González-Trujano ◽  
Eduardo Calixto González ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Depolarization ◽  
P Glycoprotein

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

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250371
Author(s):  
James W. McCormick ◽  
Lauren Ammerman ◽  
Gang Chen ◽  
Pia D. Vogel ◽  
John G. Wise
Keyword(s):  
Cell Culture ◽  
Atp Hydrolysis ◽  
Amyloid Β ◽  
Md Simulations ◽  
Membrane Transporter ◽  
Biochemical Activity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Hydrolysis Activity

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

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