An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.
Abstract
The purpose of the present study was to quantitatively elucidate the levels of protein
expression of anti-epileptic-drug (AED) transporters, metabolizing enzymes and tight
junction molecules at the blood-brain barrier (BBB) in the focal site of epilepsy
patients using accurate SWATH (sequential window acquisition of all theoretical fragment
ion spectra) proteomics. Brain capillaries were isolated from focal sites in six epilepsy
patients and five normal brains; tryptic digests were produced and subjected to SWATH
analysis. MDR1 and BCRP were significantly downregulated in the epilepsy group compared
to the normal group. Out of 16 AED-metabolizing enzymes detected, the protein expression
levels of GSTP1, GSTO1, CYP2E1, ALDH1A1, ALDH6A1, ALDH7A1, ALDH9A1 and ADH5 were significantly
2.13-, 6.23-, 2.16-, 2.80-, 1.73-, 1.67-, 2.47- and 2.23-fold greater in the brain
capillaries of epileptic patients than those of normal brains, respectively. The protein
expression levels of Claudin-5, ZO-1, Catenin alpha-1, beta-1 and delta-1 were significantly
lower, 1.97-, 2.51-, 2.44-, 1.90- and 1.63-fold, in the brain capillaries of epileptic
patients compared to those of normal brains, respectively. Consistent with these observations,
leakage of blood proteins was also observed. These results provide for a better understanding
of the therapeutic effect of AEDs and molecular mechanisms of AED resistance in epileptic
patients.
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https://hdl.handle.net/10161/25880Published Version (Please cite this version)
10.3390/pharmaceutics13122122Publication Info
Sato, Risa; Ohmori, Kotaro; Umetsu, Mina; Takao, Masaki; Tano, Mitsutoshi; Grant,
Gerald; ... Uchida, Yasuo (2021). An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters,
Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.
Pharmaceutics, 13(12). pp. 2122. 10.3390/pharmaceutics13122122. Retrieved from https://hdl.handle.net/10161/25880.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Gerald Arthur Grant
Allan H. Friedman Distinguished Professor of Neurosurgery

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