Blood–brain barrier-expressed receptor (BBB-R)

Blood-brain barrier-expressed receptors (BBB-Rs) are a specialized group of cell-surface proteins located on the luminal side of brain capillary endothelial cells (Nature Communications, 2023). These receptors, which include the transferrin receptor (TfR), insulin receptor (IR), and SLC3A2 (CD98hc), naturally facilitate the transport of essential nutrients and signaling molecules from the blood into the brain parenchyma via a process known as receptor-mediated transcytosis (RMT) (Denali Therapeutics, 2023). In the field of biotechnology, BBB-Rs are utilized as "Trojan horse" targets to overcome the restrictive nature of the blood-brain barrier, which typically prevents the entry of over 98% of large-molecule drugs (Roche, 2022). Therapeutic strategies involve engineering "transport vehicles"—such as bispecific antibodies or enzyme-fusion proteins—that bind to a BBB-R with one arm while carrying a therapeutic payload with the other (Denali Therapeutics, 2023). This binding triggers endocytosis and subsequent transport across the endothelial cell layer, releasing the drug into the central nervous system (Roche, 2022). This approach is currently being applied to develop treatments for neurodegenerative diseases like Alzheimer's and Parkinson's, as well as rare genetic disorders like Hunter syndrome (JCR Pharmaceuticals, 2021). Key challenges in targeting BBB-Rs include managing peripheral target-mediated drug disposition and ensuring that the drug does not interfere with the receptor's vital physiological functions, such as iron or glucose homeostasis (Nature Communications, 2023).

Other names

Blood-brain barrier receptorReceptor-mediated transcytosis receptorRMT receptorBrain shuttle receptorTranscytosis receptor

Receptor-mediated transcytosis (RMT) to facilitate the passage of large-molecule therapeutics across the blood-brain barrier.