PE-22-28 is a synthetic derivative of the naturally occurring protein called spadin (3). Spadin is a natural peptide derived from sortilin, an abundant protein in the central nervous system. PE-22-28 peptide is one such shortened peptide derivative of this protein; similar to spadin, PE-22-28 research indicates it primarily acts via the TREK-1 receptor.
TREK-1 (TWIK-related potassium channel) receptor is a two-pore potassium channel recently identified as a potential target for mitigating depressive symptoms. In 2010, research( 4) suggested that when TREK-1 receptors were removed from mice, they became more resistant to depression. TREK-1 receptor is primarily found in the brain region including prefrontal cortex and hippocampus, i.e., areas governing mood, memory and learning. Simulating the TREK-1 receptor may lead to reducing neuron excitability; whereas, reducing the receptor activity may lead to increasing neuron excitability (5). While mainly used in the study of antidepressant development, this receptor also plays a vital role in anesthesia, pain perception and protection of neurons.
Studies (3) in the past have suggested that naturally-occurring spadin blocks the TREK-1 channel, possibly exerting antidepressant activity for a set duration. In order to improve the bioavailability and stability, scientists conducted several studies on spadin derivatives and analogs. One such study (3) was conducted on the seven amino acid spadin derivatives called PE-22-28. PE-22-28, similar to spadin, researchers theorized that these synthetic derivatives may bind to TREK-1 channel, blocking activity and thereby producing mind stability and mood enhancement.
Since the peptide’s development, research studies have spanned a wide range of possible actions:
- potential antidepressant properties
- possible increase in the regulation of neurogenesis
- possibly improved muscle function
- possible nootropic properties
The peptide may also exhibit the following:
- possible improved stability over spadin
- possibly faster acting than other similar supposed TREK-1 blocking antidepressants
- possibly longer half life that the naturally occurring spadin
Research and Clinical Studies
PE-22-28 Peptide and Antidepressant Properties
Clinical studies have suggested that subjects with depression exhibit a smaller volume of hippocampus in the brain. When presented with the PE-22-28 compound, the smaller volume may possibly be reversed and brought to optimal level, subsequently combating depressive episodes. Researchers propose that the peptide exhibits neurogenesis potential, which is supported by the cAMP signal cascade mechanism (6).
PE-22-28 Peptide and Post Stroke Depression (PSD)
A study (5) was conducted where the experimental mice, induced with PSD syndrome, were presented with either spadin peptide or SSRI (selective serotonin reuptake inhibitors) antidepressants. SSRI, as the name suggests, is an antidepressant that is considered to prevent the reabsorption of serotonin neurotransmitters. While both compounds reportedly exhibited improvements in the mice, SSRIs induced a wide range of additional unintended actions, while PE-22-28 peptide appeared not to. The SSRI compound also reportedly took longer to exhibit any action while the peptide was apparently fast acting.
PE-22-28 Peptide and Neurogenesis
Studies have suggested that the peptide may exert neurogenesis (formation of neurons) and synaptogenesis (formation of synapse). Studies (9) were conducted where spadin derivatives were present in the neuron cultures of mice tissues. One study indicated subsequent MAPK and PI3K pathway activation, which might lead to neuron protection and formation. The other study suggested the peptide’s potential to increase in mRNA expression and concentration of brain derived neurotrophic factor (BDNF) in the hippocampus.
The hippocampus is considered to be critical for enhancing learning and memory. Hence, studies suggest that peptide PE-22-28 may exhibit nootropic properties via possible action in the hippocampus region. At a certain age, some organisms exhibit possible down regulation of CREB activity in the brain, i.e., cAMP response element binding activity. CREB is considered critical for growth and formation of neurons, and might help in memory development and neuronal plasticity. (10)
PE-22-28 Peptide and Muscle Function
TREK-1 receptor is considered also to impact the ability of muscles to respond to outer stimulation. Upon stimulation, this receptor reportedly induces relaxation of the muscles, and consequently, blocking the receptors may lead to muscle contraction. Based on this, PE-22-28 peptide is continuously being researched on to understand its potential on muscle relaxation and contraction. (11)
PE-22-28 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
1. Depression. https://medlineplus.gov/genetics/condition/depression/
2. Depression, World Health Organization. https://www.who.int/news-room/fact-sheets/detail/depression?msclkid=1b290e41ae0711ec8f12a9496f5f64ae
3. Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017 Sep 12;8:643. https://pubmed.ncbi.nlm.nih.gov/28955242/
4. Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010 Apr 13;8(4):e1000355. https://pubmed.ncbi.nlm.nih.gov/20405001/
5. Djillani, A., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Frontiers in pharmacology, 10, 379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470294/
6. Duman, R., Nakagawa, S. & Malberg, J. Regulation of Adult Neurogenesis by Antidepressant Treatment. Neuropsychopharmacol 25, 836–844 (2001). https://doi.org/10.1016/S0893-133X(01)00358-X
7. Moha Ou Maati H, Veyssiere J, Labbal F, Coppola T, Gandin C, Widmann C, Mazella J, Heurteaux C, Borsotto M. Spadin as a new antidepressant: absence of TREK-1-related side effects. Neuropharmacology. 2012 Jan;62(1):278-88. https://pubmed.ncbi.nlm.nih.gov/21807005/
8. Post Stroke Depression. https://medical-dictionary.thefreedictionary.com/post-stroke+depression
9. Devader C, Khayachi A, Veyssière J, Moha Ou Maati H, Roulot M, Moreno S, Borsotto M, Martin S, Heurteaux C, Mazella J. In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. Br J Pharmacol. https://pubmed.ncbi.nlm.nih.gov/25598009/
10. Mental health: spadin, a fast-acting antidepressant. https://journals.biologists.com/dmm/article/3/7-8/398/2435/Mental-health-spadin-a-fast-acting-antidepressant
11. Lei Q, Pan XQ, Chang S, Malkowicz SB, Guzzo TJ, Malykhina AP. Response of the human detrusor to stretch is regulated by TREK-1, a two-pore-domain (K2P) mechano-gated potassium channel. J Physiol. 2014 Jul 15;592(14):3013-30. https://pubmed.ncbi.nlm.nih.gov/24801307
NOTE: These products are intended for laboratory research use only. PE-22-28 for sale (8mg) is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.