PE-22-28

PE-22-28 is a synthetically produced peptide derived from spadin, a naturally occurring protein within sortilin—a key component of the central nervous system. Basically, PE-22-28 is a smaller, more concentrated form of spadin, and currently, what is known is that it operates primarily through its action upon the TREK-1 receptor. In fact, it is observed that PE-22-28 may be " the simplest and most effective sequence for blocking the TREK-1 channel," and more valuable as a research tool than spadin itself.

Why, then, is TREK-1 relevant? The two-pore potassium channel has been identified as one target for investigation into depression. Earlier in 2010, researchers had found that by knocking out TREK-1 receptors in mice, the mice showed increased resistance to depression behavior. TREK-1 receptors are highly prevalent in brain regions involved in mood regulation, memory, and learning, like the prefrontal cortex and the hippocampus. In simple words, stimulating TREK-1 has the effect of calming the activity of neurons, but knocking it out or impairing its function makes neurons excitable.

While the majority of studies focus on its role in depression, TREK-1 may also be involved in anesthesia, pain management, and even the protection of neurons from damage. That's why researchers continue to investigate its potential—PE-22-28 can be a very potent ally when it comes to researching and managing this fascinating receptor.

Chemical Structure

• Molecular Formula: C35H55N11O9
• Molecular Weight: 773.89 g/mol
• Sequence: GVSWGLR

Research and Clinical Studies

PE-22-28 Peptide and Depression

Research suggests that depression is commonly linked to the reduction in the volume of the hippocampus. Unexpectedly, research has also shown that administering the PE-22-28 peptide might restore lost volume, perhaps up to an optimum level. The restoration may subsequently modulate the synaptic feedback processes that increase depressive attacks. 

Scientists have identified PE-22-28's antidepressant action as being due to its capacity for inducing neurogenesis, a process mediated by the cAMP signaling cascade. Neurogenesis is a critical component of brain plasticity and offers a possible route toward improving mood and cognitive function.

PE-22-28 Peptide and Post-Stroke Depression

In a study in mice with PSD (a depression model), researchers compared the effects of the spadin peptide with a typical antidepressant—an SSRI (selective serotonin reuptake inhibitor). As might be expected, both treatments appeared to improve the mice. There were, however, some differences. SSRIs do this by inhibiting reabsorption of serotonin, so more of this "feel-good" neurotransmitter is active in the brain. Though efficient, SSRIs are known to cause a host of undesirable side effects. PE-22-28 is also believed to deliver the same benefits without such accompanying disadvantages. The second major distinction was the time it took them to work—while SSRIs take their time, the peptide worked much more rapidly. This has led scientists to consider PE-22-28 as an even more potent substitute in antidepressant research.

PE-22-28 Peptide and Post-Stroke Depression

In a study conducted on mice with PTSD ( a depression model), researchers compared the effects of the spadin peptide with a typical antidepressant, an SSRI (selective serotonin reuptake inhibitor). As might be expected, both treatments were approved to improve the condition of the mice. There were, however, some differences. SSRIs do this by inhibiting the reabsorption of serotonin. Therefore, more of this "feel-good" neurotransmitter is active in the brain. 

Though efficient, SSRIs are known to cause a lot of undesirable side effects. PE-22-28 is also believed to deliver the same benefits without such accompanying disadvantages. The second major distinction was the time it took them to work – while SSRIs take this time, the peptide worked faster. This led scientists to consider PE-22-28 as an even more potent substitute for antidepressant research. 

PE-22-28 Peptide and Neurogenesis 

Clinical trials have suggested that this peptide may exhibit synaptogenesis (formation of synapses) and neurogenesis (formation of neurons). Studies were conducted on mice, where spadin derivates were exposed in neurons. A study conducted in 2010 indicated subsequent PI3K and MARK pathway activation, which might lead to neuron formation and protection. 

Other studies indicated the peptide's ability to increase mRNA expression and concentration of BDNF or brain-derived neurotropic factor in the hippocampus. This part of the brain is crucial in memory processes and learning. 

Therefore, studies suggest that PE-22-28 may show nootropic potential through possible actions in the hippocampus region. The findings of this study suggested that spadin seems to increase the number of bromodeoxyuridine-positive cells in the hippocampus, compared to mice that were treated with saline. 

All of this hints that PE-22-28 peptide, an analog of spadin, may have a similar hippocampal neurogenesis. Spadin seems to cause a sharp rise in BrdU-positive cells within just four days, which suggests a quick activation of neurogenic pathways. 

PE-22-28 and Muscle Function

TREK-1 receptor is thought to impact muscle's ability to respond to outer stimulation. After stimulation, this receptor reportedly caused muscles to relax while blocking receptors that lead to muscle contraction. Based on what we know about this receptor, the PE-22-28 peptide is part of ongoing research linked to muscle relaxation and contraction. 

PE-22-28 and Serotonin Signaling

As previously mentioned, clinical trials indicate that PE-22-28 might function as a TREK-1 channel blocker, similar to its natural analog spadin. This belief is supported by research exploring these potential actions, mostly focusing on the connection between dorsal raphé serotonergic neurons and medial prefrontal cortex in test subjects.

The scientists noticed that spadin may stimulate serotonin neurons and concluded that serotonin actions combined with serotonin agonists seemed additive, operating independently.