PE-22-28

A synthetic heptapeptide (sequence: GVSWGLR) derived from amino acid positions 22-28 of the propeptide (PE) released during post-translational maturation of sortilin. PE-22-28 is a shortened analog of Spadin (PE 12-28) that retains full TREK-1 potassium channel inhibitory activity at approximately 333-500x greater potency. Discovered by the Mazella/Borsotto/Heurteaux group at CNRS/Université Côte d'Azur (France) as the shortest active degradation fragment of Spadin in mouse serum.

All published research originates from this single laboratory group, and no human clinical data exists. Studied exclusively in rodent models and in vitro systems for antidepressant-like effects and, more recently, stroke neuroprotection.

Published peer-reviewed research on PE-22-28 consists of two primary papers from a single French laboratory (CNRS/IPMC). Djillani et al. (2017) demonstrated antidepressant-like effects in mice across three behavioral paradigms at IC50 of 0.12 nM against TREK-1 — approximately 500x more potent than parent compound Spadin. Four-day treatment nearly doubled hippocampal neurogenesis (BrdU+ cells) and doubled PSD-95 expression.

Pietri et al. (2019) showed PE-22-28 exhibited biphasic dose-dependent action: low doses activated TREK-1 (neuroprotective) while higher doses inhibited it (antidepressant), and was reported as superior to escitalopram in preventing post-stroke depression in mice. No independent replication exists. No human clinical trials have been conducted or registered.