Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients.

Autor:	van Vliet EA; From the Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience.; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam., Iyer AM; From the Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience., Mesarosova L; From the Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience., Çolakoglu H; Division of Pharmacology, The Netherlands Cancer Institute (HÇ, OvT), Amsterdam, The Netherlands., Anink JJ; From the Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience., van Tellingen O; Division of Pharmacology, The Netherlands Cancer Institute (HÇ, OvT), Amsterdam, The Netherlands., Maragakis NJ; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland., Shefner J; Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona., Bunt T; Izumi Biosciences, Inc., Lexington, Massachusetts., Aronica E; From the Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience.
Jazyk:	angličtina
Zdroj:	Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2020 Mar 01; Vol. 79 (3), pp. 266-276.
DOI:	10.1093/jnen/nlz142
Abstrakt:	For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular distribution of the ABC transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) using immunohistochemistry in spinal cord (SC), motor cortex, and cerebellum from a large cohort of genetically well characterized ALS patients (n = 25) and controls (n = 14). The ALS group included 17 sporadic (sALS) and 8 familial (fALS) patients. Strong P-gp expression was observed in endothelial cells in both control and ALS specimens. Immunohistochemical analysis showed higher P-gp expression in reactive astroglial cells in both gray (ventral horn) and white matter of the SC, as well as in the motor cortex of all ALS patients, as compared with controls. BCRP expression was higher in glia in the SC and in blood vessels and glia in the motor cortex of ALS patients, as compared with controls. P-gp and BCRP immunoreactivity did not differ between sALS and fALS cases. The upregulation of both ABC transporters in the brain may explain multidrug resistance in ALS patients and has implications for the use of both approved and experimental therapeutics. (© 2019 American Association of Neuropathologists, Inc.)
Databáze:	MEDLINE
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