On the Amyloid-ß transcytosis across the blood-brain barrier
The blood-brain barrier (BBB) is responsible for regulating the transport of misfolded proteins to and from the Central Nervous System (CNS). One of the key players in this process is the low-density lipoprotein receptor-related protein 1 (LRP1), which is involved in the movement of several misfolded proteins, including amyloid-β (Aβ). Our research has revealed that the BBB controls the trafficking of large molecules by their affinity towards LRP1. High-affinity molecules can be retained within the endocytic pathway, while mid-affinity molecules are transported via tubular vesicles that are stabilised by the BAR domain protein, syndapin-2. We are currently investigating the role of other LRP receptors, including LRP8, and developing multivalent polymeric nanoparticles that can modulate and enhance this process to expedite the removal of Aβ.
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