PE-22-28 is a synthetic peptide derived from truncated sequences of the endogenous sortilin-associated peptide spadin. In laboratory research, PE-22-28 is utilized as a molecular tool for studying modulation of the TREK-1 (TWIK-related potassium channel-1) two-pore potassium channel and its role in regulating neuronal membrane excitability.

Experimental investigations involving PE-22-28 are restricted to in-vitro systems and in-vivo animal models, where the peptide is examined for its ability to alter ion channel conductance, intracellular signaling cascades, and cellular plasticity markers relevant to central nervous system research.

Spadin (Parent Peptide) Sequence: YAPLPRWSGPIGVSWGLR
Molecular Formula: C₉₆H₁₄₂N₂₆O₂₂
Molecular Weight: 2012.35 g/mol

PE-22-28 Sequence: GVSWGLR
Molecular Formula: C₃₅H₅₅N₁₁O₉
Molecular Weight: 773.89 g/mol

Source: PubChem

PE-22-28 is applied in experimental neuroscience and ion-channel research to evaluate TREK-1 channel inhibition, potassium conductance modulation, and downstream effects on neuronal firing dynamics.

Typical research applications include electrophysiological recordings, calcium imaging, synaptic density analysis, and transcriptional profiling in cellular cultures and rodent models.

The peptide is additionally investigated as a probe for studying neuroplasticity-associated pathways, including markers of neuronal proliferation, synapse formation, and transcription factor activation under controlled laboratory conditions.

TREK-1 is a mechanosensitive two-pore potassium channel that contributes to regulation of resting membrane potential and neuronal excitability. Inhibition of TREK-1 reduces potassium efflux, resulting in increased neuronal depolarization probability.

PE-22-28 binds TREK-1 and alters channel gating behavior, enabling mechanistic investigation of how potassium channel modulation influences excitability, synaptic transmission, and activity-dependent signaling cascades in neural tissue.

Downstream pathway analyses focus on CREB phosphorylation, synaptic protein expression, and cellular proliferation markers assessed through biochemical assays, immunohistochemistry, and gene expression profiling.

In preclinical rodent studies, PE-22-28 has been evaluated for its effects on hippocampal cell proliferation, synaptic density, and neuronal firing patterns. Experimental outcomes are measured using BrdU incorporation assays, electrophysiological recordings, and regional protein expression analyses.

Additional investigations explore TREK-1 involvement in seizure susceptibility, neuroprotection against excitotoxic stress, and modulation of mechanosensitive signaling pathways across central and peripheral tissues in animal models.

PE-22-28 is supplied as a synthetic research peptide. Identity and purity are confirmed using analytical techniques such as HPLC and mass spectrometry.

This material is intended solely for laboratory research use and is not formulated for diagnostic, medical, or clinical application.

The above literature was researched, edited and organized by Dr. E. Logan, M.D. Dr. E. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Dr. Jean Mazella obtained his PhD in 1984 from the University of Nice, France, and fulfilled the role of Assistant Professor at the Montreal Neurological Institute, Canada, from 1994-95. He is currently leading the ‘Cellular Biology of Neuropeptides and Associated Pathologies’ project at the Institute of Molecular and Cellular Pharmacology (IPMC) in France, and is Coordinator for ANR’s ENCOD (2012-14) and MEDINCOD (2014-17) programmes. His pioneering research about Spadins and the subsequent analog PE-22-28 seems to partly originate from him investigating the Sortilin/neurotensin receptor-3 system that, once knocked-out, exhibited similar effects to Spadin and PE-22-28 peptides like reduced fibrosis and higher 5-HT firing rate.

Dr. Jean Mazella is being referenced as one of the leading scientists involved in the research and development of PE-22-28. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Dr. Jean Mazella is listed in [1] under the referenced citations.

1. J. Mazella et al., “Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design,” PLoS Biol., vol. 8, no. 4, p. e1000355, Apr. 2010, doi: 10.1371/journal.pbio.1000355.
2. A. Djillani, M. Pietri, S. Moreno, C. Heurteaux, J. Mazella, and M. Borsotto, “Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity,” Front. Pharmacol., vol. 8, Sep. 2017, doi: 10.3389/fphar.2017.00643.
3. A. Djillani, J. Mazella, C. Heurteaux, and M. Borsotto, “Role of TREK-1 in Health and Disease, Focus on the Central Nervous System,” Front. Pharmacol., vol. 10, Apr. 2019, doi: 10.3389/fphar.2019.00379.
4. R. S. Duman, S. Nakagawa, and J. Malberg, “Regulation of adult neurogenesis by antidepressant treatment,” Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol., vol. 25, no. 6, pp. 836–844, Dec. 2001, doi: 10.1016/S0893-133X(01)00358-X.
5. J. E. Malberg and L. E. Schechter, “Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs,” Curr. Pharm. Des., vol. 11, no. 2, pp. 145–155, 2005, doi: 10.2174/1381612053382223.
6. N. Katalinic, R. Lai, A. Somogyi, P. B. Mitchell, P. Glue, and C. K. Loo, “Ketamine as a new treatment for depression: a review of its efficacy and adverse effects,” Aust. N. Z. J. Psychiatry, vol. 47, no. 8, pp. 710–727, Aug. 2013, doi: 10.1177/0004867413486842.
7. H. Moha Ou Maati et al., “Spadin as a new antidepressant: absence of TREK-1-related side effects,” Neuropharmacology, vol. 62, no. 1, pp. 278–288, Jan. 2012, doi: 10.1016/j.neuropharm.2011.07.019.
8. C. Devader et al., “In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin,” Br. J. Pharmacol., vol. 172, no. 10, pp. 2604–2617, May 2015, doi: 10.1111/bph.13083.
9. A. J. Silva, J. H. Kogan, P. W. Frankland, and S. Kida, “CREB and memory,” Annu. Rev. Neurosci., vol. 21, pp. 127–148, 1998, doi: 10.1146/annurev.neuro.21.1.127.
10. T. C. of B. Limited, “Mental health: spadin, a fast-acting antidepressant,” Dis. Model. Mech., vol. 3, no. 7–8, pp. 398–398, Jul. 2010.
11. Q. Lei, X.-Q. Pan, S. Chang, S. B. Malkowicz, T. J. Guzzo, and A. P. Malykhina, “Response of the human detrusor to stretch is regulated by TREK-1, a two-pore-domain (K2P) mechano-gated potassium channel,” J. Physiol., vol. 592, no. 14, pp. 3013–3030, Jul. 2014, doi: 10.1113/jphysiol.2014.271718.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATONAL AND EDUCATIONAL PURPOSES ONLY.

The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body.  These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease.  Bodily introduction of any kind into humans or animals is strictly forbidden by law.

For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.