Figures & data
Figure 1. The mechanisms by which human pathogens and the toxins they secrete achieve CNS entry include: (1) receptor- and non-receptor mediated transcytosis, (2), paracellular transport, (3), carriage within immune cells, (4) retrograde transport from the periphery, and (5) entry through regions of altered BBB permeability, such as those found in the choroid plexus of the cerebral ventricles or olfactory neurons.
Table 1. Examples of neurotropic viruses and their receptors
Table 2. Pathogenic ligands known to bind to 37/67kDa receptor (LamR)
Table 3. Three-finger toxins that specifically target nAChR and have been associated with BBB penetration
Table 4. Conopeptides that specifically interact with nAChR and are associated with BBB penetration
Figure 2. Bio-inspired nanocarriers can be engineered to improve drug delivery to the CNS. In this example, a solid polymer nanoparticle encapsulates a therapeutic (small molecule, nucleic acid, or protein) or imaging agent. The surface of the viral-sized nanoparticle is modified to display a pathogen-derived peptide (e.g., rabies virus glycoprotein) that will facilitate passage of nanoparticle with cargo across the BBB. Therapeutic compounds that have been encapsulated in biodegradable nanoparticles will be released slowly over time for targeted treatment. A solid polymer nanoparticle is shown as one example of a targeted drug carrier; many other types of carriers or conjugates can be similarly modified to improve CNS delivery (for example, liposomes, micelles, drug-antibody conjugates, and othersCitation115).
Table 5. Examples of CNS-directed delivery achieved by pathogenic strategies