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Mamma Mia, P-glycoprotein binds again

Callaghan, Richard; Gelissen, Ingrid; George, Anthony M.; Hartz, Anika M. S.

Description

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...[Show more]

dc.contributor.authorCallaghan, Richard
dc.contributor.authorGelissen, Ingrid
dc.contributor.authorGeorge, Anthony M.
dc.contributor.authorHartz, Anika M. S.
dc.date.accessioned2021-03-19T01:16:45Z
dc.identifier.issn0014-5793
dc.identifier.urihttp://hdl.handle.net/1885/227564
dc.description.abstractThe 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.
dc.description.sponsorshipThe project was supported by grant number 2R01AG039621 from the National Institute on Aging (to AMSH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherElsevier
dc.rights© 2020 Federation of European Biochemical Societies
dc.sourceFEBS Letters
dc.source.urihttps://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.13951
dc.subjectABCB1
dc.subjectAlzheimer’s disease
dc.subjectamyloid peptides
dc.subjectblood–brain barrier
dc.subjecthydrophobic peptides
dc.subjectMDR1
dc.subjectmembrane transport
dc.subjectPgp
dc.titleMamma Mia, P-glycoprotein binds again
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolumeOnline
dc.date.issued2020
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.absfor060110 - Receptors and Membrane Biology
local.identifier.absfor060112 - Structural Biology (incl. Macromolecular Modelling)
local.identifier.ariespublicationa383154xPUB13950
local.publisher.urlhttps://febs.onlinelibrary.wiley.com
local.type.statusPublished Version
local.contributor.affiliationCallaghan, Richard, College of Science, ANU
local.contributor.affiliationGelissen, Ingrid, University of Sydney
local.contributor.affiliationGeorge, Anthony M., University of Technology Sydney
local.contributor.affiliationHartz, Anika M. S., University of Kentucky
local.description.embargo2099-12-31
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage9
local.identifier.doi10.1002/1873-3468.13951
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
dc.date.updated2020-11-22T07:19:02Z
local.identifier.scopusID2-s2.0-85092891105
CollectionsANU Research Publications

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