PE 22-28 10mg*10vials

▎PE 22-28 Structure

▎PE 22-28 Research

What is the research background of PE 22-28?  

Research on PE 22-28 originated from the exploration of therapeutic targets for depression. In 2006, the TREK-1 protein was identified as a potential target for depression treatment. Studies showed that deleting the TREK-1 gene in mice enhanced serotonin neurotransmission efficiency, rendering them resistant to depression, and significantly reduced corticosterone levels under stress, indicating that inhibiting this channel might be used for depression treatment. Subsequent research found that the Sortilin protein regulates TREK-1 channel activity, and Sortilin and TREK-1 are highly expressed in brain regions associated with depression, providing a direction for antidepressant drug development.  

Against this backdrop, researchers designed the peptide Spadin (PE 12-28) in 2010 to test its regulation of the TREK-1 channel and antidepressant potential. Through in-depth studies on short analogs of Spadin, the 7-amino-acid peptide PE 22-28 (Mini-Spadin) was successfully synthesized in 2017. Its research and development journey represents a continuous search for effective inhibitors of the TREK-1 channel for depression treatment.  

What is the mechanism of action of PE 22-28?

Effects on the TREK-1 Channel  

High Specificity and Affinity: In vitro studies using patch-clamp techniques on hTREK-1/HEK cells showed that PE 22-28 exhibits better specificity and affinity for the TREK-1 channel compared to Spadin. Specifically, PE 22-28 has an IC₅₀ (half-maximal inhibitory concentration) of 0.12 nM, while Spadin has an IC₅₀ of 40–60 nM. This indicates that PE 22-28 can more effectively bind to the TREK-1 channel, thereby regulating its function ^[1].  

Channel Activity Regulation: Under the same experimental conditions, studies have shown that different modifications at the N or C terminus of PE 22-28 can maintain or eliminate TREK-1 channel activity without affecting its affinity for the TREK-1 channel. This suggests that TREK-1 channel activity can be precisely regulated by modifying the termini of PE 22-28, providing a direction for further optimizing its therapeutic effects. For example, specific modifications may enhance its inhibitory effect on the channel, thereby more effectively regulating related neural signaling pathways^[1].  

Effects in In Vivo Antidepressant Behavior Models

Forced Swim Test: In the forced swim test, a depression behavior model, mice treated with PE 22-28 and its derivatives showed a significant reduction in immobility time. Immobility time is an important indicator of depression-like behavior in mice; reduced immobility time indicates alleviation of depression-like behavior, suggesting that PE 22-28 and its derivatives can improve depression-related behavior in vivo and possess antidepressant activity ^[1].  

Novelty-Suppressed Feeding Test: In the novelty-suppressed feeding test after 4 days of subchronic treatment, PE 22-28 significantly reduced the latency of mice to consume food pellets. The novelty-suppressed feeding test reflects anxiety and depression states in mice; shortened latency indicates relief of anxiety and depression, further confirming the antidepressant effect of PE 22-28 in vivo ^[1].

Figure 1 Spadin-analog specificity. (A–D) PE 22-28 was used as the representative peptide for testing the specificity of spadin-analogs vs. other K2P channels, TREK-2 (A), TRAAK (B), TRESK (C), and TASK-1 (D).

Source:PubMed^[1]

Effects on Neurogenesis and Synaptogenesis

Induction of Neurogenesis: After just 4 days of treatment, PE 22-28 and its analogs can induce neurogenesis, with G/A-PE 22-28 showing a particularly significant effect. Neurogenesis is crucial for maintaining normal nervous system function and coping with mental disorders, and depression patients often exhibit impaired neurogenesis. PE 22-28 can promote neurogenesis, helping repair damaged neural functions and improve depressive symptoms ^[1].  

Enhancement of Synaptogenesis: In mouse cortical neurons, PE 22-28 and its derivatives enhance synaptogenesis, as measured by increased expression levels of PSD-95 (postsynaptic density protein 95). Increased PSD-95 expression indicates enhanced synaptic quantity or function. Enhancing synaptogenesis can improve information transmission between neurons and optimize neural circuit function, which is of great significance for alleviating depressive symptoms^[1].  

Superior Duration of Action: Compared to Spadin, the duration of action of PE 22-28 and its analogs has been significantly improved, extending from 7 hours for Spadin to 23 hours. The longer duration of action allows PE 22-28 to more stably regulate the TREK-1 channel and promote neurogenesis and synaptogenesis in vivo, thereby more effectively maintaining antidepressant effects, reducing dosing frequency, and improving patient compliance ^[1].  

What are the applications of PE 22-28?  

Antidepressant Effects: Depression is a mental disorder affecting numerous people worldwide, and existing antidepressants suffer from delayed onset and severe side effects. PE 22-28 and its derivatives have significant potential in depression treatment. Studies have shown that in depression behavior models such as the forced swim test, mice treated with Spadin-analogs (including PE 22-28) exhibited significantly reduced immobility time, indicating improved depression-related behavior. In the novelty-suppressed feeding test, after 4 days of subchronic treatment, PE 22-28 significantly reduced the latency to consume food pellets, further confirming its alleviation of depressive symptoms. After just 4 days of treatment, PE 22-28 and its analogs can induce neurogenesis, with G/A-PE 22-28 showing a prominent effect. In mouse cortical neurons, they also enhance synaptogenesis, as measured by increased PSD-95 expression. Compared to the previous endogenous peptide Spadin with antidepressant activity, PE 22-28 exhibits better specificity and affinity for the TREK-1 channel (IC₅₀ of 0.12 nM vs. 40–60 nM for Spadin) and a significantly extended duration of action from 7 to 23 hours, making PE 22-28 more promising in depression treatment ^[1].

Potential Expansion to Nervous System Disease Treatment: Given the positive effects of PE 22-28 on neurogenesis and synaptogenesis, it may have potential applications in treating other nervous system diseases. The pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease is closely related to abnormalities in neurogenesis and synaptic function. PE 22-28 may provide new ideas and methods for treating these diseases by regulating neurogenesis and synaptic plasticity.  

Potential for Combination with Other Treatments: In depression treatment, single-drug therapy may not meet the needs of all patients. PE 22-28 can be considered for combination with existing antidepressants, leveraging its rapid onset and positive effects on neural plasticity to compensate for the delayed onset of traditional antidepressants and potentially reduce traditional drug dosages, thereby lowering side effects. Additionally, it can be combined with psychotherapy such as cognitive behavioral therapy to improve patient symptoms from both pharmacological and psychological intervention perspectives, enhancing treatment efficacy.  

Conclusion  

In summary, PE 22-28 holds significant application potential in the medical field, currently primarily as a potential candidate molecule for treating depression. It can improve depression-like behavior, induce neurogenesis, and offers faster onset and longer-lasting effects compared to traditional antidepressants.

About The Author

The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.

Scientific Journal Author

Djillani, Alaeddine is a distinguished scholar in the life sciences and medical fields. Collaborating with renowned institutions like the University of Washington, Universite Cote d'Azur, and Universite Paris Saclay, his research spans a wide array of disciplines, including Pharmacology & Pharmacy, Cell Biology, Neurosciences & Neurology, Biochemistry & Molecular Biology, and Physiology. These areas are crucial for understanding fundamental life processes, disease mechanisms, and new drug development. His work has yielded significant results in basic sciences and offers vital theoretical and practical guidance for medical applications and clinical practice. This underscores his exceptional ability and broad influence in interdisciplinary research.. Djillani, Alaeddine is listed in the reference of citation [1].

▎Relevant Citations

[1]  Djillani A, Pietri M, Moreno S, et al. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and  Antidepressant Activity[J]. Frontiers in Pharmacology, 2017,8:643.DOI:10.3389/fphar.2017.00643.

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