What Is PE-22-28 Peptide?
PE-22-28 is a synthetic variant of the naturally occurring peptide spadin. Spadin is a secreted peptide obtained from sortilin. It acts as an antagonist of the TREK-1 (TWIK-related-potassium channel) receptor, a two-pore potassium channel identified as a potential target in treating depression and as a possible neurogenic regulator. Studies in mice have shown that TREK-1 receptor deletion makes them resistant to depression. Sortilin treatment also leads to resistance to depression by promoting neuronal growth and intersynaptic connections.
PE-22-28 represents the group of synthetic spadin analogs with higher efficacy and stability than spaldin.
Neurogenesis is a long-term consequence of consuming anti-depressant medications (e.g., SSRIs) is neurogenesis. Neuronal growth indicates the efficacy of anti-depressants. PE-22-28 is faster than any known anti-depressant and induces neurogenesis after just four days. The peptide can treat neurodegenerative diseases, stroke, and boost memory.
TREK-1 is found in various tissues such as the brain, heart, smooth muscle, pancreas and plays important roles in pain perception, anesthesia, and neuroprotection.
AKA: Spadin Analog, PE2228, TREK-1 Antagonist, PE 22 28, Sortilin Derivative, PE 2228
Molecular Formula: C35H55N11O9
Molecular Weight: 773.8947 g/mol
What Is TREK-1?
It is the cognate receptor for spadin and thus PE-22-28 primarily. It is a two-pore potassium channel regulated by several different molecules and regulates neuronal excitability. TREK-1 is abundant in the prefrontal cortex, the amygdala, and the hippocampus. By reducing the neuron’s excitability, TREK-1 can help protect against excitotoxicity.
PE-22-28 is more effective in reversing depression than any currently used treatment and with fewer side effects. It has been shown to relieve depression in just four days without producing any side effects on other functions that are controlled by the TREK-1 channel.
PE-22-28 reverses the loss of hippocampal volume by stimulating neurogenesis and thus helps fight depression.
The peptide does not show any significant side effects which are commonly associated with anti-depressant medication. Current treatments for depression have a host of known side effects ranging from suicidality to libido changes and cognition problems. PE-22-28 promotes neurogenesis without triggering these side effects.
Post-stroke depression (PSD) is a common symptom of post-brain ischemia and affects standard treatment caused by TREK-1 overexpression. In experimental mouse models, this upregulation can be suppressed or reversed using both SSRI anti-depressants as well as TREK-1 blockers like spadin.
PE-22-28 promotes neurogenesis but in a shorter duration of time. Studies in mice reveal that PE-22-28 increases neurogenesis and synaptogenesis after four days.
CREB (cAMP response element-binding protein) is a transcription factor associated with neuronal plasticity, memory formation, and the development of spatial memory. CREB appears to be a necessary component in not just the growth of neurons but also in their protection.
Now, it has generally been demonstrated in animal models that removing the TREK-1 channel is a recipe for disaster. In previous mouse models, knockout of TREK-1 increased the likelihood of seizure activity significantly and reduced the normal ability of this two-pore potassium channel to protect neurons from excitotoxicity. It came as a bit of surprise then that neither spadin nor PE-22-28 enhanced seizure activity. Even more interesting is the fact that mice treated with spadin are more resistant to developing generalized seizures. PE-22-28 has even more profound protective effects than spadin.
There is some research to suggest that TREK-1 plays an important role in the ability of a muscle to respond to mechanical stimulation. In particular, TREK-1 blockade appears to increase contractility in muscle tissue, while activation of the channel appears to promote muscle relaxation. While this particular aspect of the TREK-1 channel is still in the early stages of the investigation, it is becoming increasingly important. There is hope that understanding the role of molecules like PE-22-28 in muscle contraction and relaxation may provide new treatment modalities for conditions like myogenic bladder dysfunction and may also open up new pathways for understanding the physiology of muscle performance.
PE-22-28 is an effective treatment for depression and a potent stimulator of neurogenesis and synaptogenesis in the hippocampus. It has far fewer side effects than existing anti-depressant medications. It appears to retain much of its ability to antagonize TREK-1 even after modifications that boost half-life or alter the route of administration. In short, PE-22-28 thus provides a strong target for guiding the development of a new generation of anti-depressants and is helping to shed light on the burgeoning field of nootropics. It is also helping to expand the arsenal of medications used to treat neurodegenerative diseases like Alzheimer’s disease.
Only buy PE-22-28 peptide if you are a licensed researcher.