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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00730

Homeostatic peptides and their long-term action on neurological energy metabolism: Teneurin C-terminal associated peptide (TCAP) as a model for a therapeutic peptide.

 David Lovejoy1*, David W. Hogg2, Fernando S. Jurado2, Casey C. Read2,  Thomas Dodsworth2,  Andrea L. D'Aquila2 and Dalia Barsyte-Lovejoy2
  • 1Department of Cell and Systems Biology, University of Toronto, Canada
  • 2University of Toronto, Canada

Teneurins are multifunctional transmembrane proteins that bind to the latrophilins, which are 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. The teneurins possess a cleavable peptide unit on their extracellular face that interacts with the latrophilins and plays a number of roles in the inhibition of the corticotropin-releasing factor (CRF) -associated stress response. This peptide, known as teneurin C-terminal associated peptide (TCAP), has structural similarity to CRF, and its related peptides, such as calcitonin and the secretin-based peptides. Moreover, its receptor, latrophilin is structurally related to the secretin family of GPCRs. TCAP is a soluble peptide that enters the brain and efficaciously 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, because TCAP is efficacious at blocking CRF action in vitro and in vivo, 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 mood disorders.

Keywords: stress, Blood brain - barrier, Corticotroin-releasing factor, G-protein couple receptor, evolution

Received: 17 Apr 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Lovejoy, Hogg, Jurado, Read, Dodsworth, D'Aquila and Barsyte-Lovejoy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. David Lovejoy, University of Toronto, Department of Cell and Systems Biology, Toronto, M5S 3G5, Ontario, Canada,