PE-22-28 Research

PE-22-28 is a synthetic derivative of the naturally occurring peptide Spadin, which binds to TREK-1, a protein found in areas of the brain that control mood, memory, and learning. It is being investigated for its potential benefits in treating depression, improving memory and learning, aiding stroke recovery, and potentially combating neurodegenerative diseases such as Alzheimer’s.

PE-22-28 and Treatment of Depression

PE-22-28 has shown promising results in the treatment of depression. The peptide specifically blocks the TREK-1 channel, a mechanism that has been linked to antidepressant activity. In comparison to spadin, PE-22-28 has demonstrated better specificity and affinity for the TREK-1 channel, with an IC50 (half maximal inhibitory concentration) of 0.12 nM versus 40-60 nM for spadin.

In behavioral models of depression, such as the forced swimming test, mice treated with PE-22-28 showed a significant reduction in immobility time, indicating an antidepressant effect. Furthermore, PE-22-28 was found to have improved in vivo stability and bioavailability compared to spadin, maintaining its activity for up to 23 hours instead of 7 hours.

PE-22-28 Stimulates Neurogenesis and Synaptogenesis

PE-22-28 has been found to stimulate neurogenesis and synaptogenesis, processes crucial for the formation and functioning of neural networks. In a study, PE-22-28 and its analogs were able to induce neurogenesis after only a 4-day treatment. On mouse cortical neurons, PE-22-28 and its derivatives enhanced synaptogenesis, as measured by the increase of PSD-95 expression level, a protein critical for synaptic maturation and function. This suggests that PE-22-28 could potentially be used to promote the formation and strengthening of neural connections.

PE-22-28 and Post-Stroke Recovery

Research presented in 2018 and published the following year demonstrated that chronic treatment with PE-22-28 improved post-stroke recovery for months after the ischemia. Treated mice showed a significant reduction in immobility time in the Forced Swimming Test, and the latency to eat in the Novelty Suppressed Feeding test was also reduced. This suggests that PE-22-28 may prove effective in future trials exploring the treatment of post-stroke depression .

PE-22-28 May Improve Muscle Function

Research suggests that PE-22-28 may promote muscle relaxation. TREK-1, a receptor that PE-22-28 binds to, plays a vital role in a muscle’s ability 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 .

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