Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ analysis
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ analysis
Adult
Aged
Amyotrophic Lateral Sclerosis
/ metabolism
Astrocytes
/ metabolism
Cerebellum
/ metabolism
Female
Humans
Male
Middle Aged
Motor Cortex
/ metabolism
Neoplasm Proteins
/ analysis
Spinal Cord
/ metabolism
Amyotrophic lateral sclerosis (ALS)
Astrocytes
BCRP
Blood vessels
Motor cortex
Multidrug resistance
P-glycoprotein (P-gp)
Spinal cord
Journal
Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
15
06
2019
revised:
23
11
2019
accepted:
20
12
2019
pubmed:
31
1
2020
medline:
22
7
2020
entrez:
31
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31999342
pii: 5718003
doi: 10.1093/jnen/nlz142
pmc: PMC7036662
doi:
Substances chimiques
ABCG2 protein, human
0
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
266-276Informations de copyright
© 2019 American Association of Neuropathologists, Inc.
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