Research ArticleNeuroscience

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

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Science Signaling  05 Oct 2010:
Vol. 3, Issue 142, pp. ra72
DOI: 10.1126/scisignal.2001213

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Getting Drugs into the Brain and Keeping Them There

Delivery of potentially therapeutic drugs to the brain after a stroke is impeded by changes in the abundance of two transporters found on endothelial cells in brain capillaries. The abundance of ABCB1, which is found on the luminal side of cerebral capillaries and transports drugs from brain to blood, increases with ischemia. In contrast, the abundance of ABCC1, which is found on the abluminal (“brain”) side of cerebral capillaries and transports drugs from blood to brain, decreases. ElAli and Hermann showed that these changes in transporter abundance depended on apolipoprotein E (ApoE) signaling through its receptor ApoE receptor–2 (ApoER2). They found ApoE associated with ischemic brain capillaries but not nonischemic capillaries. Moreover, they showed that ApoER2 was preferentially localized to the abluminal surface of brain capillary endothelial cells, which suggests that it might act as a sensor for brain ischemia. The discovery that ApoE signaling through ApoER2 regulates the abundance of ABCB1 and ABCC1 suggests that inhibition of this pathway could enable the enhanced delivery of neuroprotective drugs to the brain after ischemic stroke.

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