Back to Search
Start Over
MDR1-P-Glycoprotein (ABCB1) Mediates Transport of Alzheimer’s Amyloid-β Peptides—Implications for the Mechanisms of Aβ Clearance at the Blood–Brain Barrier.
- Source :
- Brain Pathology; Oct2007, Vol. 17 Issue 4, p347-353, 7p, 5 Graphs
- Publication Year :
- 2007
-
Abstract
- Amyloid-β (Aβ) is the major component of the insoluble amyloid plaques that accumulate intracerebrally in patients with Alzheimer’s disease (AD). It has been suggested that MDR1-P-glycoprotein (ABCB1, P-gp) plays a substantial role in the elimination of Aβ from the brain. In the present study, MDR1-transfected LLC cells growing in a polarized cell layer were used to characterize the interaction of Aβ1-40/1-42 with P-gp. In this system, P-gp-mediated transport can be followed by the efflux of the fluorescent dye rhodamine-123, or of Aβ itself from the cells into the apical extracellular space. Aβ significantly decreased the apical efflux of rhodamine-123, and the transcellular transport of Aβ1-40 and Aβ1-42 into the apical chamber could be demonstrated using both ELISA and fluorescence (FITC)-labeled peptides. This transport was inhibited by a P-gp modulator. Furthermore, ATP-dependent, P-gp-mediated transport of the fluorescence-labeled peptides could be demonstrated in isolated, inside-out membrane vesicles. Our data support the concept that P-gp is important for the clearance of Aβ from brain, and thus may represent a target protein for the prevention and/or treatment of neurodegenerative disorders such as AD. [ABSTRACT FROM AUTHOR]
- Subjects :
- P-glycoprotein
PEPTIDES
ALZHEIMER'S disease
AMYLOID
BRAIN diseases
Subjects
Details
- Language :
- English
- ISSN :
- 10156305
- Volume :
- 17
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Brain Pathology
- Publication Type :
- Academic Journal
- Accession number :
- 26913714
- Full Text :
- https://doi.org/10.1111/j.1750-3639.2007.00075.x