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Mamma Mia, P‐glycoprotein binds again
Author(s) -
Callaghan Richard,
Gelissen Ingrid C.,
George Anthony M.,
Hartz Anika M. S.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13951
Subject(s) - glycoprotein , peptide , membrane glycoproteins , amyloid (mycology) , p glycoprotein , chemistry , transporter , biochemistry , membrane , blood–brain barrier , amyloid precursor protein , microbiology and biotechnology , biophysics , biology , alzheimer's disease , neuroscience , central nervous system , gene , medicine , disease , inorganic chemistry , multiple drug resistance , antibiotics
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.