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Sci. Signal., 5 October 2010
Vol. 3, Issue 142, p. ra72
[DOI: 10.1126/scisignal.2001213]

RESEARCH ARTICLES

Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain

Ayman ElAli and Dirk M. Hermann*

Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

Abstract: The adenosine triphosphate–binding cassette transporters ABCB1 and ABCC1 show coordinated changes in abundance at the luminal and abluminal membranes of ischemic cerebral capillaries that impede the brain access of pharmacological compounds. We found that apolipoprotein E (ApoE) was present on ischemic microvessels but not contralateral controls. ApoE signaled through ApoE receptor–2 (ApoER2), which was constitutively expressed on brain microvessels, to decrease c-Jun amino-terminal kinase 1 and 2 and c-Jun activities. ApoE regulated the postischemic abundance of ABCB1 and ABCC1, thereby controlling drug accumulation in the ischemic brain. Our data suggest that inhibition of ApoE signaling may enable improved delivery of drugs to the brain.

* To whom correspondence should be addressed. E-mail: dirk.hermann{at}uk-essen.de

Citation: A. ElAli, D. M. Hermann, Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain. Sci. Signal. 3, ra72 (2010).

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