title: Retroinverso analogs of spadin display increased antidepressant effects.
abstract: BACKGROUND
  Although depression is the most common mood disorder, only one third of patients are treated with success. Finding new targets, new drugs, and also new drug intake way are the main challenges in the depression field. Several years ago, we identified a new target with the TWIK-related potassium channel-1 (TREK-1) potassium channel, and more recently, we have discovered a peptide of 17 amino acids with antidepressant properties. This peptide, that we called spadin, can be considered as a new concept in antidepressant drug design. Spadin derives from a larger peptide resulting to a posttranslational maturation of sortilin; consequently, spadin can be considered as a natural molecule. Moreover, spadin acts more rapidly than classical antidepressants and does not induce side effects.
  
  
  OBJECTIVE
  In this work, we sought analogs of spadin displaying a better affinity on TREK-1 channels and an increased action duration.
  
  
  METHODS
  Analogs were characterized by electrophysiology measurements, by behavioral tests, and by their ability to induce neurogenesis.
  
  
  RESULTS
  We identified two retro-inverso peptides that have kept the antidepressant properties of spadin; particularly, they increased the hippocampal neurogenesis after a 4-day treatment. As spadin, these analogs did not induce side effects on either pain, epilepsy processes, or at the cardiac level.
  
  
  CONCLUSIONS
  Together, our results indicated that spadin retro-inverso peptides could represent new potent antidepressant drugs. As exemplified by spadin in the field of depression, retro-inverso strategies could represent a useful technique for developing new classes of drugs in a number of pathologies.
authors: Université de Nice Sophia Antipolis, IPMC, 06560, Sophia Antipolis, France.
authors: Julie
authors: J
authors: Veyssiere
authors: Hamid
authors: H
authors: Moha Ou Maati
authors: Jean
authors: J
authors: Mazella
authors: Georges
authors: G
authors: Gaudriault
authors: Sébastien
authors: S
authors: Moreno
authors: Catherine
authors: C
authors: Heurteaux
authors: Marc
authors: M
authors: Borsotto
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy*; D015195:Drug Design; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000032:analysis* / Q000494:pharmacology*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D010455:Peptides; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C551795:spadin peptide