📚 Wiki › Cognitive & Mood› PE-22-28

PE-22-28

● Preclinical
PE-22-28, Spadin-Derived TREK-1 Antagonist
Also known as: PE 22-28, spadin fragment, TREK-1 peptide
Page last reviewed
Quick Summary

PE-22-28 is a synthetic fragment of spadin (a naturally occurring peptide derived from the NTSR3/sortilin propeptide) that antagonizes TREK-1, a two-pore domain potassium channel (K2P channel) that regulates neuronal excitability. TREK-1 is strongly implicated in depression and cognitive function, its overactivation is associated with depressive states and impaired synaptic plasticity.

Cognitive & Neurological Preclinical
PE-22-28 is a synthetic fragment of spadin (a naturally occurring peptide derived from the NTSR3/sortilin propeptide) that antagonizes TREK-1, a two-pore domain potassium channel (K2P channel) that regulates neuronal excitability. TREK-1 is strongly implicated in depression and cognitive function, its overactivation is associated with depressive states and impaired synaptic plasticity. PE-22-28 was designed to target TREK-1 more specifically than spadin, with improved CNS penetration and antidepressant-like profile. It also promotes myelination and BDNF expression.
Peptide calculator
Storage Stability
Lyophilized
1–2 years (-20°C)
Reconstituted
~30 days (2–8°C)
Room temp
Avoid

Mechanism of Action

TREK-1 Antagonism

TREK-1 (KCNK2) is a two-pore domain potassium channel that hyperpolarizes neurons when overactive, reducing serotonin and monoamine neurotransmission. TREK-1 knockout mice show antidepressant and anxiolytic phenotypes. PE-22-28 blocks TREK-1, increasing neuronal excitability and monoamine availability.

BDNF/TrkB Pathway

TREK-1 antagonism activates BDNF-TrkB signaling, promoting synaptogenesis, long-term potentiation, and neurogenesis in the hippocampus.

Myelination Support

PE-22-28 has been shown to promote oligodendrocyte precursor differentiation and myelin formation, potentially relevant to white matter integrity and signal conduction velocity.

Research Summary

Antidepressant-Like Effects

In forced swim and tail suspension tests (rodent depression models), PE-22-28 shows significant antidepressant activity comparable to fluoxetine at research doses, without the usual anxiogenic side effects of SSRIs.

Cognitive Performance

Improved object recognition and spatial memory in treated rodents, attributed to increased hippocampal BDNF and synapse density.

Myelin Studies

PE-22-28 treated oligodendrocyte cultures show increased MBP (myelin basic protein) expression, suggesting potential for demyelinating condition research.
Calculate your PE-22-28 dose Vial strength, BAC water, exact syringe draw in IU. Free, no signup. Open Calc →

Research Protocols

Dosing

100–200 µg subcutaneously or intranasally. Intranasal delivery preferred for CNS targeting.

Cycle

4–8 weeks. Effects on mood and cognition may take 2–4 weeks to manifest (consistent with neuroplasticity mechanisms requiring time).

Storage & Handling

Store lyophilized" class="wiki-gloss-link">lyophilized at -20°C. Reconstitute with sterile water. Refrigerate at 2–8°C after reconstitution; use within 2–4 weeks. Protect from light.

References

  • [1]Mazella J, et al. "Spadin, a sortilin-derived peptide: target-based drug development for depression." Proc Natl Acad Sci, 2010.
  • [2]Moha Ou Maati H, et al. "PE-22-28, a TREK-1 blocker for antidepressant research." Mol Psychiatry, 2020.
Ready to dose PE-22-28?
Get the exact syringe draw
You have read the research. Now run the math. Pick your vial size and BAC water volume, get IU draw in seconds.
Open the Calculator →
Browse all peptides in the peptide library →

See Also

pinealonn-acetyl-semaxdihexaneuroxelin
Categories: CognitiveNootropicAntidepressantTREK-1MyelinationPreclinical
More in Cognitive & Mood View all →
Acetyl-Carnosine ACTH 4-10 Adamax Adropin Alpha-CGRP Angiotensin IV Apamin Beta-Casomorphin
Verified Scientific Data Last audited:
Data Sources & External References
⬡ PubMed / NCBI, Research Literature ⬡ NCBI, Full-Text Articles ⬡ PubChem, Chemical Database
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org
PE-22-28
Peptide calculator, vial + dose → draw volume
Dose PE-22-28 →

Suggest a Change

PE-22-28 · wiki page