Mamma Mia, P-glycoprotein binds again

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4076-4084
Number of pages9
JournalFEBS Letters
Volume594
Issue number23
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 Federation of European Biochemical Societies

Keywords

  • ABCB1
  • Alzheimer’s disease
  • MDR1
  • Pgp
  • amyloid peptides
  • blood–brain barrier
  • hydrophobic peptides
  • membrane transport

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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