1. Petersburg Institute of Nuclear Physics of Russian Academy of Sciences 2. State Research Institute of Highly Pure Biopreparations 3. Division of Neurology, Duke University Medical Center 4. Petersburg Institute of Nuclear Physics of Russian Academy of Sciences Institute for Experimental Medicine of Russian Academy of Medical Sciences
Protein transduction domain (PTD)-peptides greatly facilitate the delivery of high molecular weight macromolecules across the blood-brain barrier (BBB). This BBB-transport function is highly desirable and helps to enable the development of new therapeutics for treatment of brain disorders. However, the drug discovery process is limited by the generation of a simple and reliable BBB model that is amenable to testing of large number of samples and simultaneously, reproduces the physiological and functional characteristics of the human BBB. To address these challenges, we have studied whether the PTD-peptide penetratin, derived from a Drosophila Antennapedia homeodomain protein, is capable of crossing the BBB in Drosophila while carrying a cargo into the fly brain. An initial in vivo experiment in Drosophila showed that abdominal injection of biotin-tagged penetratin permeated the BBB. The same effect was observed for biotin-tagged penetratin fused with apoE mimetic peptide with demonstrated anti-inflammatory and neuroprotective activities.