Apolipoprotein E controls ATP-binding cassette transporters in the ischemic brain

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Updated: Jun 8, 2026

Isolation of Cerebral Capillaries from Fresh Human Brain Tissue
06:35

Isolation of Cerebral Capillaries from Fresh Human Brain Tissue

Published on: September 12, 2018

Ayman ElAli1, Dirk M Hermann

  • 1Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

Science Signaling
|October 7, 2010
PubMed

Insights

Apolipoprotein E (ApoE) signaling in ischemic brain capillaries affects drug transporter abundance, hindering brain drug delivery. Inhibiting ApoE signaling may improve therapeutic access to the brain.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Adenosine triphosphate-binding cassette transporters (ABCB1 and ABCC1) are crucial for regulating drug permeability across the blood-brain barrier.
  • Ischemic stroke alters the expression and localization of these transporters, limiting the efficacy of brain-targeted therapeutics.

Purpose of the Study:

  • To investigate the role of apolipoprotein E (ApoE) in regulating the abundance of ABCB1 and ABCC1 transporters in ischemic cerebral capillaries.
  • To explore the potential of targeting ApoE signaling pathways to enhance drug delivery to the ischemic brain.

Main Methods:

  • Immunohistochemical analysis of ischemic and contralateral cerebral microvessels to detect apolipoprotein E (ApoE) and ApoE receptor-2 (ApoER2) expression.
  • Assessment of c-Jun N-terminal kinase (JNK) activity in response to ApoE signaling.
  • Quantification of ABCB1 and ABCC1 transporter abundance in post-ischemic brain tissue.

Main Results:

  • Apolipoprotein E (ApoE) was found on ischemic microvessels but not in control tissues.
  • ApoE signaling, via ApoE receptor-2 (ApoER2), reduced c-Jun N-terminal kinase (JNK) activity.
  • ApoE modulated the post-ischemic abundance of ABCB1 and ABCC1, influencing drug accumulation in the brain.

Conclusions:

  • Apolipoprotein E (ApoE) plays a significant role in regulating drug transporter expression in the ischemic brain.
  • Inhibiting ApoE signaling presents a potential therapeutic strategy to overcome drug delivery barriers in ischemic stroke.

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