To what extent do cell-penetrating peptides selectively cross the blood-brain barrier?

The blood-brain barrier protects the brain from toxic compounds. Its selective permeability is essential for the optimal function of the central nervous system. Some peptides can cross the blood-brain barrier. On the other hand, cell-penetrating peptides are able to overcome the cell membrane. During this research project, it was investigated whether these cell-penetrating peptides also can cross the blood-brain barrier. The chemical diversity of the already reported cell-penetrating peptides was investigated and a unified response for the extent of cellular uptake of peptides was introduced. Based on this study, a set of cell-penetrating peptides was rationally selected for further research. In order to more objectively compare the quantitative data on the blood-brain barrier influx of peptides, a classification system for blood-brain barrier influx was established. The purity of the selected synthetized cell-penetrating peptides was also investigated, which is essential for obtaining reliable research conclusions. Different chromatographic systems were compared for the analysis of the selected peptides. The investigated cell-penetrating peptides crossed the blood-brain barrier to a different extent. The influx varied from very low to very high and some peptides showed efflux out of the brain. There was no correlation observed between the blood-brain barrier transport kinetics and the extent of cellular uptake. During the aging process, the blood-brain barrier shows an increased permeability and, together with other age-related functional changes, should be taken into account during the development of medicines used by the elderly. Therefore, the current regulatory status of the development of geriatric medicines was investigated.

ISBN:9789461973085

Jaar van publicatie:2015

Toegankelijkheid:Open