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. 2019 Apr 11;10:379. doi: 10.3389/fphar.2019.00379

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Copyright © 2019 Djillani, Mazella, Heurteaux and Borsotto.

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.

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Polymodal TREK-1 regulation. TREK-1 is multiregulated by a variety of physical and chemical stimuli. TREK-1 possesses different protein partners such as AKAP150, β-COP, Mtap2, and sortilin. Sortilin interacts with TREK-1 an address it to the plasma membrane. Spadin is a synthetic peptide derived from sortilin which was shown to block TREK-1 with high affinity. Spadin antidepressant activity appears to be mediated through PI3K and Akt activation. TREK-1 is involved in numerous CNS pathologies such as depression, ischemia, epilepsy and pain.