Peptide Family Promotes Brain Cell Rejuvenation and Improved Cognition through Peripheral Delivery.

Ligands targeting folate receptor α (FRα), a protein predominantly expressed in neural cells, have the potential to reprogram (rejuvenate) brain cells and enhance cognitive function in aged mice. In this study, we present a family of FRα-binding peptides identified through AlphaFold modeling. These peptides induce a structural change in the receptor upon binding, which facilitates its internalization and transport to the cell nucleus. Once in the nucleus, FRα functions as a transcription factor, promoting the expression of genes associated with a youthful phenotype and improved cognition. Notably, these peptides demonstrate permeability across the blood-brain barrier, enabling their administration not only through intracranial injection but also via peripheral delivery methods such as intraperitoneal injection or gastric gavage. This property enhances their potential for use in future therapeutic applications.