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 language | English |
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Pages (from-to) | 4076-4084 |
Number of pages | 9 |
Journal | FEBS Letters |
Volume | 594 |
Issue number | 23 |
DOIs | |
State | Published - Dec 2020 |
Bibliographical note
Funding Information:The 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.
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