Trinity compound research profile
PE-22-28
PE 22-28 is a lab-made peptide made of just 7 amino acids. It's a shortened version of a slightly longer natural peptide called spadin, which itself comes...
Research overview
PE 22-28 is a lab-made peptide made of just 7 amino acids. It's a shortened version of a slightly longer natural peptide called spadin, which itself comes from a piece cut off a larger protein called sortilin. The exact letter sequence of its 7 amino acids hasn't been printed in the original scientific publication, so it isn't fully confirmed from that source (Djillani et al., Front Pharmacol 2017).
Mechanism under study
Nerve cells have tiny pores (channels) that control electrical activity, and one specific pore called TREK-1 tends to dampen down the activity of mood-related brain cells (serotonin neurons) when it's open. PE 22-28 works by blocking this TREK-1 pore, similar to plugging a hole, which makes those mood-related brain cells more active and encourages the growth of new brain cell connections (spadin original report, PLoS Biol 2010). It's roughly 400–600 times more powerful at this specific blocking job than its parent molecule spadin, and importantly, it doesn't seem to affect several other similar pore types tested, meaning it's fairly selective (Front Pharmacol 2017).
Human evidence summary
There is no human clinical trial of PE 22-28. The closest thing to human data is an indirect study measuring how levels of the related sortilin-derived propeptide change in people's blood after they receive electroconvulsive therapy for depression (study) — but that's not the same as testing PE 22-28 itself in people.
Preclinical evidence summary
In mice, small doses (3.0–4.0 micrograms per kilogram of body weight, given into the belly) reduced signs of depression-like behavior in a standard test where mice are placed in water and their struggling is measured — treated mice struggled almost twice as long compared to untreated mice, suggesting less 'giving up' behavior, a marker researchers associate with antidepressant effects (Front Pharmacol 2017). The same study found it nearly doubled the growth of new brain cells in a memory-related brain region after 4 days of treatment. However, one other research group found conflicting evidence questioning exactly how selectively spadin (the parent molecule) really targets its intended pore, raising some doubt about the precise mechanism (Ma & Lewis 2020).
Source material
Use the linked publications and records to evaluate study design, population, limitations, and relevance.