Spadin, a Sortilin-derived peptide: a new concept in the antidepressant drug design

Institut de pharmacologie moléculaire et cellulaire, CNRS, Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France

^* heurteaux@ipmc.cnrs.fr

Abstract

Depression is the most common of psychiatric illnesses. The design of effective treatments for this disorder is a challenging process. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. Deletion of TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate the fast antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the sortilin receptor and acting through TREK-1 inhibition.