Journal
FEBS LETTERS
Volume 594, Issue 23, Pages 4076-4084Publisher
WILEY
DOI: 10.1002/1873-3468.13951
Keywords
ABCB1; Alzheimer's disease; amyloid peptides; blood-brain barrier; hydrophobic peptides; MDR1; membrane transport; Pgp
Funding
- National Institute on Aging [2R01AG039621]
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The levels of amyloid peptides in the brain are regulated by a clearance pathway from neurons to the blood-brain barrier. The first step is thought to involve diffusion from the plasma membrane to the interstitium. However, amyloid peptides are hydrophobic and avidly intercalate within membranes. The ABC transporter P-glycoprotein is implicated in the clearance of amyloid peptides across the blood-brain, but its role at neurons is undetermined. We here propose that P-glycoprotein mediates 'exit' of amyloid peptides from neurons. Indeed, amyloid peptides have physicochemical similarities to substrates of P-glycoprotein, but their larger size represents a conundrum. This review probes the plausibility of a mechanism for amyloid peptide transport by P-glycoprotein exploiting evolving biochemical and structural models.
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