Modulating LRP1 and LRP8 in the blood-brain barrier using multivalent nanomedicines
The blood-brain barrier (BBB) plays a main role in regulating the transport of misfolded proteins from and into the CNS. Two of the different receptors involved have been singled out: the low-density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2. Several data suggest a primary role of LRP1 in the shuttling of amyloid-β (Aβ) across the BBB. To stimulate such a physiological process, we formulate functionalised polymeric nanoparticles whose avidity, based on multiple ligand-receptor affinities, can reproduce what happens in vivo. To support our theory, we evaluate the expression of the main genes involved in the transcytosis and deeply characterise our BBB in vitro model. The investigations herein are an important step to further assess the enhancement of the clearance of Aβ from the CNS by using polymeric nanoparticles.
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