Applications of ApoB LDLR-binding domain approach for the development of CNS-penetrating peptides for Alzheimer'Ss disease

Abstract

Delivery of protein therapeutics to the CNS has proven to be a challenge to due to the presence of the blood-brain barrier (BBB), which prevents the passage of most proteins and large molecules from invading the neuronal space. Recently, we, and others, have developed technologies to circumvent this barrier by targeting receptors on the surface of the endothelial cells of the BBB to facilitate transport of therapeutic proteins. We describe here one such approach for targeting the LDLR by fusion of 38 amino acids from the ApoB protein to a therapeutic protein.