PE-22-28

Not FDA-approved

Also known as: Mini-spadin

Structure source: Human sortilin propeptide residues 22-28 (UniProt Q99523, precursor residues 55-61)

PE-22-28 is a lab-made chain of seven amino acids copied from a natural fragment of sortilin, a protein in the body. It is a shortened version of spadin, a longer peptide studied for depression. It showed antidepressant-like effects in mice, but no study has tested it in people.

How it works

In lab studies, it blocks TREK-1, a potassium channel that keeps nerve cells from firing too easily.
In lab tests on cells carrying human TREK-1, it blocked the channel far more strongly than spadin.
In mice, short courses reduced behaviours used to screen antidepressant drugs and increased the growth of new nerve cells.
In a mouse stroke model, it reduced movement and thinking problems and prevented depression-like behaviour. Low amounts switched TREK-1 on, while higher amounts blocked it.
In lab tests on insulin-making pancreatic cells, it helped the cells survive inflammatory damage.

Evidence

Depression and mood

Animal and lab studies onlyCEBM Level 5

In mice, it reduced depression-like behaviour in standard screening tests. No study has given it to people, and no trial is registered.

Recovery after stroke

Animal and lab studies onlyCEBM Level 5

In mice with an induced stroke, it reduced movement and thinking problems and prevented depression-like behaviour. It has not been studied in people with stroke.

Caveats

No study has given PE-22-28 to people. Its safety, side effects and effective dose in humans are unknown.
Human studies often linked to it measured the body's own sortilin fragment in the blood of depressed patients. They did not give the peptide.
TREK-1 also works in the heart, pain nerves and insulin-making cells. Mice lacking TREK-1 were more prone to seizures, had heart-rhythm pauses under stress, and handled blood sugar worse on a high-fat diet. Whether PE-22-28 does any of this is unknown.
Most of the research comes from one French group. An independent lab found that spadin, the parent peptide, did not directly block TREK-1 in its test system.
Its interactions with antidepressants and other psychiatric medicines have not been studied.

References

Reviewed by Shubham Gupta, MD — Founder & President · October 31, 2026

This page is for education only. It is not medical advice. Decisions about any treatment belong with a physician who knows your history.