Abstract
The pharmacological treatment of central nervous system diseases faces significant challenges due to the presence of the blood-brain barrier (BBB). This barrier naturally protects the brain and prevents therapeutics from reaching their targets efficiently. However, the BBB allows the passage of nutrients and other molecules that guarantee brain homeostasis through selective transport mechanisms present at the BBB. These mechanisms provide an opportunity for delivering therapeutic agents into the central nervous system using brain shuttles. Here we review the progress of brain shuttle peptide development from 2015 until 2025. We highlight the most utilized peptides and describe trends in strategies to develop new shuttles and enhance their transport efficiency. Additionally, we compared them with other types of brain shuttles and emphasize the progress of peptide shuttles toward clinical translation.