Title : In vitro modeling of the blood-brain barrier to assess CNS drug delivery
The blood-brain barrier (BBB) is located at the brain microvessel level and isolates the brain from the whole body, thus restricting molecule and cell exchanges between cerebral and peripheral compartments. BBB physiology is altered in Alzheimer’s disease (AD) mainly characterized by an abnormal accumulation of amyloid peptides in brain and by an altered brain cholesterol homeostasis. For a long time, the BBB was basically considered as a barrier isolating the brain from circulating cholesterol, however, several lines of evidence now suggest that the BBB strictly regulates the exchanges of sterol and mayloid between the brain and the peripheral circulation. Oxysterols, synthesized by neurons or by peripheral cells, cross the BBB easily and modulate the expression of several enzymes, receptors, and transporters which are involved not only in cholesterol metabolism but also in other brain functions. This talk deals with the way oxysterols impact BBB cells, and in particular Liver X signaling pathway (LXR) and its targer genes such as ABCA1. These perspectives open new routes for designing certain therapeutical approaches that target the BBB so that the onset and/or progression of brain diseases such as AD may be modulated.
Audience take away:
• Alterations of the blood-brain barrier physiology occurring in Alzheimer’s disease will be presented.
• Molecular mechanisms regulating the cholesterol and the amyloid exchanges between brain and periphery will be presented and discussed.
• Consequences of LXR activation on these both processes will be discussed.
• Perspectives on therapeutical approaches targeting the BBB will be highlighted.