Brain endothelial LRP1 maintains blood–brain barrier integrity

Fluids and Barriers of the CNS

Claus U. Pietrzik¹  Steffen E. Storck¹  Magdalena Kurtyka¹ 

[1] Molecular Neurodegeneration, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Duesbergweg 6, 55099, Mainz, Germany;

关键词: Blood–brain barrier integrity;    Low-density lipoprotein receptor-related protein 1 (LRP1);    P-glycoprotein/Abcb1 (P-gp);    Tight junctions;    Matrix metalloproteinases (MMPs);    Cyclophillin A;   

DOI  :  10.1186/s12987-021-00260-5

来源: Springer

【 摘 要 】

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-CreERT2 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.

【 授权许可】

CC BY