Journal
FLUIDS AND BARRIERS OF THE CNS
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12987-021-00260-5
Keywords
Blood-brain barrier integrity; Low-density lipoprotein receptor-related protein 1 (LRP1); P-glycoprotein; Abcb1 (P-gp); Tight junctions; Matrix metalloproteinases (MMPs); Cyclophillin A
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Funding
- Deutsche Forschungsgemeinschaft [PI 379/8-3]
- IMI EU grant (Im2pact)
- University Medical Center of the Johannes-Gutenberg University Mainz
- Projekt DEAL
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The blood-brain barrier regulates the entry of blood-borne molecules into the brain to maintain brain homeostasis. The protein LRP1 plays a key role in controlling the paracellular passage of blood proteins into the brain through the formation of tight junctions.
The entry of blood-borne molecules into the brain is restricted by the blood-brain barrier (BBB). Various physical, transport and immune properties tightly regulate molecule movement between the blood and the brain to maintain brain homeostasis. A recent study utilizing a pan-endothelial, constitutive Tie2-Cre showed that paracellular passage of blood proteins into the brain is governed by endocytic and cell signaling protein low-density lipoprotein receptor-related protein 1 (LRP1). Taking advantage of conditional Slco1c1-CreER(T2) specific to CNS endothelial cells and choroid plexus epithelial cells we now supplement previous results and show that brain endothelial Lrp1 ablation results in protease-mediated tight junction degradation, P-glycoprotein (P-gp) reduction and a loss of BBB integrity.
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