Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers
Peptides play a major role in the transmission of information to and from the central nervous system. However, because of their structural complexity, the development of pharmacological peptide-based therapeutics has been challenged by the lack of understanding of endogenous peptide evolution. The t...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-11-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00730/full |
| _version_ | 1819087888450584576 |
|---|---|
| author | David A. Lovejoy David A. Lovejoy David W. Hogg Thomas L. Dodsworth Fernando R. Jurado Casey C. Read Andrea L. D'Aquila Andrea L. D'Aquila Dalia Barsyte-Lovejoy |
| author_facet | David A. Lovejoy David A. Lovejoy David W. Hogg Thomas L. Dodsworth Fernando R. Jurado Casey C. Read Andrea L. D'Aquila Andrea L. D'Aquila Dalia Barsyte-Lovejoy |
| author_sort | David A. Lovejoy |
| collection | DOAJ |
| description | Peptides play a major role in the transmission of information to and from the central nervous system. However, because of their structural complexity, the development of pharmacological peptide-based therapeutics has been challenged by the lack of understanding of endogenous peptide evolution. The teneurin C-terminal associated peptides (TCAP) possess many of the required attributes of a practical peptide therapeutic. TCAPs, associated with the teneurin transmembrane proteins that bind to the latrophilins, members of the Adhesion family of G-protein-coupled receptors (GPCR). Together, this ligand-receptor unit plays an integral role in synaptogenesis, neurological development, and maintenance, and is present in most metazoans. TCAP has structural similarity to corticotropin-releasing factor (CRF), and related peptides, such as calcitonin and the secretin-based peptides and inhibits the (CRF)-associated stress response. Latrophilins are structurally related to the secretin family of GPCRs. TCAP is a soluble peptide that crosses the blood-brain barrier and regulates glucose transport into the brain. We posit that TCAP represents a phylogenetically older peptide system that evolved before the origin of the CRF-calcitonin-secretin clade of peptides and plays a fundamental role in the regulation of cell-to-cell energy homeostasis. Moreover, it may act as a phylogenetically older peptide system that evolved as a natural antagonist to the CRF-mediated stress response. Thus, TCAP's actions on the CNS may provide new insights into the development of peptide therapeutics for the treatment of CNS disorders. |
| first_indexed | 2024-12-21T21:43:18Z |
| format | Article |
| id | doaj.art-db6812fca58943b6ba590ee180e4d169 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T21:43:18Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-db6812fca58943b6ba590ee180e4d1692022-12-21T18:49:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-11-011010.3389/fendo.2019.00730462201Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain BarriersDavid A. Lovejoy0David A. Lovejoy1David W. Hogg2Thomas L. Dodsworth3Fernando R. Jurado4Casey C. Read5Andrea L. D'Aquila6Andrea L. D'Aquila7Dalia Barsyte-Lovejoy8Department of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaProtagenic Therapeutics Inc., New York, NY, United StatesDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaDepartment of Pediatrics, University of Alabama, Birmingham, AL, United StatesStructural Genomics Consortium, University of Toronto, Toronto, ON, CanadaPeptides play a major role in the transmission of information to and from the central nervous system. However, because of their structural complexity, the development of pharmacological peptide-based therapeutics has been challenged by the lack of understanding of endogenous peptide evolution. The teneurin C-terminal associated peptides (TCAP) possess many of the required attributes of a practical peptide therapeutic. TCAPs, associated with the teneurin transmembrane proteins that bind to the latrophilins, members of the Adhesion family of G-protein-coupled receptors (GPCR). Together, this ligand-receptor unit plays an integral role in synaptogenesis, neurological development, and maintenance, and is present in most metazoans. TCAP has structural similarity to corticotropin-releasing factor (CRF), and related peptides, such as calcitonin and the secretin-based peptides and inhibits the (CRF)-associated stress response. Latrophilins are structurally related to the secretin family of GPCRs. TCAP is a soluble peptide that crosses the blood-brain barrier and regulates glucose transport into the brain. We posit that TCAP represents a phylogenetically older peptide system that evolved before the origin of the CRF-calcitonin-secretin clade of peptides and plays a fundamental role in the regulation of cell-to-cell energy homeostasis. Moreover, it may act as a phylogenetically older peptide system that evolved as a natural antagonist to the CRF-mediated stress response. Thus, TCAP's actions on the CNS may provide new insights into the development of peptide therapeutics for the treatment of CNS disorders.https://www.frontiersin.org/article/10.3389/fendo.2019.00730/fullstresslatrophilinreceptor-ligand interactionneuroplasticityblood-brain barrierG-protein coupled receptors |
| spellingShingle | David A. Lovejoy David A. Lovejoy David W. Hogg Thomas L. Dodsworth Fernando R. Jurado Casey C. Read Andrea L. D'Aquila Andrea L. D'Aquila Dalia Barsyte-Lovejoy Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers Frontiers in Endocrinology stress latrophilin receptor-ligand interaction neuroplasticity blood-brain barrier G-protein coupled receptors |
| title | Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers |
| title_full | Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers |
| title_fullStr | Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers |
| title_full_unstemmed | Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers |
| title_short | Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers |
| title_sort | synthetic peptides as therapeutic agents lessons learned from evolutionary ancient peptides and their transit across blood brain barriers |
| topic | stress latrophilin receptor-ligand interaction neuroplasticity blood-brain barrier G-protein coupled receptors |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00730/full |
| work_keys_str_mv | AT davidalovejoy syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT davidalovejoy syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT davidwhogg syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT thomasldodsworth syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT fernandorjurado syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT caseycread syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT andrealdaquila syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT andrealdaquila syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers AT daliabarsytelovejoy syntheticpeptidesastherapeuticagentslessonslearnedfromevolutionaryancientpeptidesandtheirtransitacrossbloodbrainbarriers |