Bell et al. find that APOE3 — which does not trigger BBB dysfunction — binds to a receptor protein (LRP1) on the surface of pericytes and, by doing so, prevents the inflammatory response. By contrast, in mice expressing APOE4 or lacking any APOE proteins, this interaction does not occur, and the resulting inflammatory response breaks down the BBB. The authors' findings suggest that APOE4 cannot bind to LRP1 as efficiently as does APOE3, and so fails to 'cool down' the brain pericytes. Of note, the researchers show that the APOE4-triggered changes in the BBB precede neurological deterioration in the mice studied. Moreover, chemical inhibitors of this pro-inflammatory pathway healed the breached BBB and ameliorated the neuronal changes in the animals, opening up the possibility of improved treatment of Alzheimer's disease.
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A (Bell et al. 2012)
http://www.ncbi.nlm.nih.gov/
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