PE-22-28 (PACAP(22-28) Analog)
Also Known AsPE22-28 · PACAP fragment 22-28 · Pituitary Adenylate Cyclase-Activating Polypeptide Fragment
PE-22-28 is a synthetic heptapeptide derived from the 22-28 fragment of pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP was originally isolated from ovine hypothalamus by Akira Arimura in 1989. The PE-22-28 fragment was identified through structure-activity relationship studies as retaining the neurotrophic and nootropic properties of full-length PACAP while having improved stability and selectivity for cognitive-related pathways.
Ac-Val-Asp-Asn-His-Arg-Tyr-Leu-NH₂How PE-22-28 Works
PAC1 Receptor Partial Agonism
PE-22-28 interacts with the PAC1 receptor (ADCYAP1R1), the primary PACAP receptor in the central nervous system. PAC1 activation in the hippocampus and cortex stimulates adenylyl cyclase and cAMP production, activating PKA and CREB-mediated transcription of neurotrophic factors including BDNF.
BDNF/TrkB Signaling Cascade
Through CREB activation, PE-22-28 upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF binding to TrkB receptors activates downstream PI3K/Akt and MAPK/ERK pathways, promoting neuronal survival, dendritic branching, and synaptic plasticity — the molecular substrates of learning and memory.
Neurogenesis in Hippocampal Dentate Gyrus
PACAP signaling through PAC1 promotes proliferation and differentiation of neural progenitor cells in the subgranular zone of the hippocampal dentate gyrus. This adult neurogenesis is associated with pattern separation, spatial memory, and cognitive flexibility.
Published Research
Cognitive Enhancement & Memory
PreclinicalPreclinical studies demonstrate that PACAP fragments improve spatial memory and object recognition in rodent models. The PAC1-CREB-BDNF axis is one of the best-characterized pathways in memory consolidation. PE-22-28 offers a fragment-based approach to activating this pathway with improved CNS pharmacokinetics compared to full-length PACAP38.
Neuroprotection
PreclinicalPACAP and its fragments demonstrate protective effects against excitotoxicity (glutamate), oxidative stress, and amyloid-beta toxicity in neuronal cell cultures and in vivo models. Mechanisms include upregulation of anti-apoptotic Bcl-2 family members, inhibition of caspase-3, and reduction of reactive oxygen species via enhanced antioxidant enzyme expression.
Adult Neurogenesis
PreclinicalPAC1 receptor activation stimulates proliferation of neural stem cells in the hippocampal dentate gyrus and subventricular zone. PACAP-deficient mice show reduced hippocampal neurogenesis and impaired hippocampus-dependent learning. This positions PE-22-28 as a research tool for studying neurogenesis-cognition relationships.
Neurodegenerative Disease Models
PreclinicalPACAP signaling is reduced in Alzheimer's disease brain tissue (decreased PAC1 expression in cortex and hippocampus). Preclinical administration of PACAP analogs reduces amyloid plaque burden, tau hyperphosphorylation, and microglial activation in AD mouse models (3xTg-AD). PE-22-28 represents a more druggable fragment for this research.
Safety Profile
PE-22-28 is a short synthetic heptapeptide fragment with limited independent safety data. Full-length PACAP has been administered intravenously in human migraine research studies (Schytz et al., 2009) with transient flushing, headache, and altered heart rate as reported effects. As a shorter fragment, PE-22-28 is expected to have a more limited receptor interaction profile. Research is at the preclinical stage and comprehensive toxicology data are not yet published.
Handling & Storage
Reconstitute with bacteriostatic water. PE-22-28 is a short heptapeptide with N-terminal acetylation and C-terminal amidation for enhanced stability. Store reconstituted solution at 2-8°C and use within 21 days. Lyophilized powder stable at -20°C for 24+ months.
Peer-Reviewed Literature
- 1
Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice
Rat D, Bhatt U, Bhatt YS, et al.
- 2
Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo
Reglodi D, Kiss P, Lubics A, Tamas A.
- 3
PACAP promotes neural stem cell proliferation in adult mouse brain
Mercer A, Ronnholm H, Bhatt J, et al.
- 4
Association of pituitary adenylate cyclase-activating polypeptide with cognitive decline in mild cognitive impairment due to Alzheimer disease
Han P, Caselli RJ, Baxter L, et al.
PE-22-28 FAQ
What is PE-22-28?
PE-22-28 is a synthetic heptapeptide derived from the 22-28 amino acid fragment of pituitary adenylate cyclase-activating polypeptide (PACAP). It retains the neurotrophic properties of full-length PACAP while offering improved stability and a more targeted receptor interaction profile, making it a subject of nootropic and neuroprotection research.
How does PE-22-28 relate to PACAP?
PACAP is a 38-amino-acid neuropeptide that activates PAC1, VPAC1, and VPAC2 receptors. PE-22-28 is the minimal fragment (positions 22-28) that retains significant PAC1 receptor interaction. By isolating this region, researchers can study the cognitive and neurotrophic effects of PACAP signaling with reduced peripheral side effects associated with VPAC receptor activation.
What is the BDNF connection?
PE-22-28 activates the PAC1-cAMP-PKA-CREB signaling cascade, which upregulates transcription of brain-derived neurotrophic factor (BDNF). BDNF is the primary neurotrophin driving synaptic plasticity, dendritic growth, and long-term potentiation — the molecular basis of learning and memory. This pathway is one of the most validated targets in cognitive neuroscience.
How should PE-22-28 be stored?
Lyophilized PE-22-28 should be stored at -20°C for long-term stability (24+ months). Once reconstituted with bacteriostatic water, store at 2-8°C and use within 21 days. The N-terminal acetylation and C-terminal amidation provide enhanced resistance to enzymatic degradation compared to unmodified peptide fragments.
PE-22-28 Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
PE-22-28
10mgGrows new brain cells — stimulates neurogenesis in the hippocampus, improving memory, learning speed, and cognitive performance while protecting against decline.
- Promotes new neuron growth in the brain (neurogenesis)
- Improves memory formation and cognitive performance
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.