What it is
PE-22-28 is a peptide made of 7 amino acids. It is made in a lab. It is the shortest working piece of spadin, a 17 amino acid peptide the body makes. Spadin comes from sortilin, a protein in brain cells. PE-22-28 blocks TREK-1, a potassium channel that keeps brain cells quiet. Mice bred without TREK-1 resist depression-like behavior. Scientists at a French national research center (CNRS) designed it. Other names: Mini-Spadin, PE 22-28, GVSWGLR.
What researchers study it for
- Depression-like behavior in mice
- Blocking the TREK-1 channel
- New brain cell growth in the hippocampus
- Recovery after stroke in mice
What the studies found
1. It blocked TREK-1 about 300 times more strongly than spadin and lasted longer.
A 2017 study tracked how spadin breaks down in mouse blood and tested the pieces. PE-22-28 blocked TREK-1 about 300 times more strongly than spadin. It did not block four related channels. Its effect in mice lasted up to 23 hours, compared with about 7 hours for spadin. Mice showed less depression-like behavior, and new hippocampal cells nearly doubled after 4 days. Lab cell and mouse data.
2. The parent peptide spadin worked in mice only when TREK-1 was present.
A 2010 study found spadin blocks TREK-1. Mice given spadin showed less depression-like behavior in several tests. Serotonin nerve cells fired more. Spadin had no effect in mice bred without TREK-1, which shows it acts through that channel. This study tested spadin, not PE-22-28. Mouse data only.
3. Very small amounts protected mice after stroke. Larger amounts blocked depression-like behavior.
A 2019 study gave PE-22-28 to mice after a stroke. At very small amounts, it turned TREK-1 on instead of blocking it. That protected against weight loss and delayed nerve cell loss. At larger amounts, it blocked TREK-1 and reduced depression-like behavior after the stroke. The effect flips depending on the amount. Mouse data only.
4. An outside lab found spadin blocks TREK-1 in a specific way.
Arachidonic acid is a fat that turns TREK-1 on. A 2020 study from a separate lab found spadin blocks only this type of TREK-1 activation. It does this by changing the channel's shape, not by plugging it. This study tested spadin, the parent peptide. Lab cells only.
5. Depressed patients who improved after ECT had more of the parent protein in their blood.
ECT, or electroconvulsive therapy, is a treatment for severe depression. A 2018 study measured the sortilin piece that spadin comes from in 45 patients whose depression had not improved with other treatments. Levels rose about 1 month after ECT, but only in patients who improved. No one was given PE-22-28. Human observational data.
How much research exists
A small set of lab and mouse studies. Almost all come from one French research group. No human has been given PE-22-28 in a published study.
Facts
- Formula: C35H55N11O9
- Weight: about 774 g/mol
- CAS number: 1801959-12-5 (could not confirm)
- Sequence: Gly-Val-Ser-Trp-Gly-Leu-Arg
- Time in the blood: never measured. Its effect in mice lasted up to 23 hours.
- Storage: no tested storage data. Similar peptides are kept as powder in the freezer.
Legal status
Not approved by the FDA or any other agency for any use.
For research use only. Not for human use. Nothing here is medical advice.