What is PE-22-28?
PE-22-28 is a seven-amino-acid peptide created by French researchers who study spadin. Spadin is a peptide based on a piece that is cut off when cells process a protein called sortilin. The name PE-22-28 refers to its position: it matches amino acids 22 to 28 of the sortilin propeptide, the piece of sortilin that spadin comes from. Spadin itself is 17 amino acids long, and PE-22-28 keeps the part that appears to matter for its activity.
The goal was a peptide that blocks TREK-1 like spadin does, but that lasts longer in the body. In the published mouse and cell work, PE-22-28 was reported to block TREK-1 more strongly and to stay active longer than spadin. All of this research is preclinical, and PE-22-28 has not been developed as an approved medicine.
How does PE-22-28 work?
TREK-1 is a potassium channel, a pore in the membrane of nerve cells that helps keep them in a resting state. It is found in brain regions tied to mood, memory and stress. In earlier mouse studies, mice bred without TREK-1 showed fewer depression-like behaviors, which pointed to TREK-1 as a possible target for antidepressants. Spadin and PE-22-28 block this channel. In mouse studies of spadin, this was linked to faster firing of serotonin-producing nerve cells and to the growth of new nerve cells in the hippocampus.
What has research looked at?
- Depression-like behavior
- In mouse behavior tests, PE-22-28 and related analogs reduced depression-like behaviors. The effects were reported after only a few days of treatment, which is faster than standard antidepressants act in similar mouse models.
- New nerve cells
- In mice, treatment with spadin and its shortened analogs was linked to more new nerve cells forming in the hippocampus, a change that has also been seen with other antidepressant treatments.
- Stability and strength
- In lab and mouse studies, PE-22-28 lasted longer and blocked TREK-1 more strongly than the original spadin.
- Learning and stress
- Online sources often claim benefits for learning, stress resilience or stroke recovery. These claims rest on early animal research on spadin, its analogs and TREK-1, and have not been shown for PE-22-28 in people.
The evidence is early. All published work on PE-22-28 comes from cell and mouse studies, mainly by the research group that designed it. Many treatments that look promising in mouse models of depression do not work in people, so these findings are a starting point, not a result.
Side effects and cautions
Because PE-22-28 has not been tested in published human studies, its side effects in people are unknown. Statements that it has no side effects, or that it is safer than antidepressants, are not supported by human data. Depression is a serious medical condition with established treatments. Anyone struggling with low mood, or thinking about stopping or changing a medicine, should talk to a qualified clinician.
- TREK-1 has protective roles
- In mouse studies, TREK-1 also appeared to help protect nerve cells during seizures and reduced blood flow. Researchers have asked whether blocking it could carry risks, and this has not been tested in people.
- Antidepressants and other medicines
- How PE-22-28 might interact with antidepressants or other brain-active medicines is unknown.
- Pregnancy and breastfeeding
- There are no safety data for pregnancy or breastfeeding.
Further reading
This page summarizes the research in plain words. To read the studies yourself:
- Published studies on PE-22-28 PubMed, US National Library of Medicine
