Peptides are short (typically less than 5000 Da) chains of two or more amino acids with many important biological functions. Many peptides function as hormones and regulate aspects of feeding, metabolism, sleep, stress, immunity, mood, and reproduction. Over 5000 endogenous peptides with known biological functions have been identified, and many of these can cross intact barriers of the central nervous system (CNS), such as the endothelial blood-brain barrier (BBB) or epithelial blood-cerebrospinal fluid barrier (BCSFB). Peptide therapies reflected a major medical advancement of the 20th century, beginning with the use of insulin to treat diabetes. Presently, there are over 80 approved peptide therapies, many of which target the hormonal activities of endogenous peptides, and others that are derived from toxins or microbial peptides. The extent to which brain barriers regulate the CNS entry and activities of endogenous and therapeutic peptides is an active area of study and an important consideration in peptide drug development.

Over the last 40 years, major advances in recombinant DNA technologies, structural biology, and synthetic and analytical approaches have revolutionized peptide drug development. Currently, some major challenges in this field include 1) limiting the peripheral effects of bioactive peptides while sufficiently activating CNS targets, 2) improving in vivo stability, 3) elucidating mechanisms of peptide entry into the brain, 4) identifying novel functions of peptides in the CNS, 5) identifying and/or engineering CNS-targeting peptides with improved efficacy, and 6) understanding the biological and pathophysiological variables such as aging, sex, and disease states that could modulate the CNS distribution of endogenous and therapeutic peptides. The goal of this Research Topic is to bring new knowledge and insight to the field of CNS peptide therapeutics, particularly focusing on the involvement of brain barriers as regulatory interfaces for CNS peptide delivery.

We welcome submissions of original research, brief communications, review, and mini-review articles that focus on peptide transport into and action within the CNS. Topics of particular interest include, but are not limited to, the following:
- Newly discovered peptides that act within the CNS
- Transport of peptides into the CNS and mechanisms involved
- Novel peptide activities within the CNS
- Novel delivery methods of peptides into the CNS
- New technology and/or methods applicable to the design, development, and analysis of CNS peptide delivery
- Studies of biological and/or pathophysiological variables that influence the CNS disposition of endogenous or therapeutic peptides

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Frontiers in Drug Delivery

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