This PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused or mislabled as a drug, food or cosmetic.

What is PE-22-28?

PE-22-28 is a synthetic derivative of the naturally occurring peptide spadin. Spadin is a secreted peptide derived from sortilin. It is an antagonist of the TREK-1 (TWIK-related-potassium channel) receptor, a two-pore potassium channel identified as a potential target in the treatment of depression and as a possible neurogenic regulator. Early studies in mice have shown that a deletion of the TREK-1 receptor makes them resistant to depression. Similarly, treatment with sortilin leads to resistance to depression boosts the growth of both neurons and the synaptic interconnections between neurons[1].

Interestingly, shortened analogs of spadin actually show better TREK-1 inhibition than spadin itself. PE-22-28 is the representative peptide for this group of synthetic spadin analogs. PE-22-28 has been shown to be more stable and have improved antidepressant activity and neurogenic properties over the naturally occurring spadin.

It is important to note that one of the long-term consequences of taking anti-depressant medications (e.g. SSRIs) is neurogenesis. In fact, the growth of new neurons is considered to be one indication that depression is being adequately treated and that antidepressants are working. PE-22-28 has been shown to induce neurogenesis after just 4 days, which is substantially faster than any known antidepressant. This also suggests that PE-22-28 might be useful in other applications such as learning, stroke recovery, and perhaps even the battle against neurodegenerative diseases[2].

TREK-1, which is primarily found in the brain, is also found in the heart, smooth muscle cells, lung tissue, the prostate, and in specific areas of the pancreas. Though it has been primarily studied as a target for antidepressant activity, TREK-1 plays important roles in pain perception, anesthesia, and neuroprotection. These properties have made TREK-1 a major research target in academia and industry.

Structures

Spadin Sequence: YAPLPRWSGPIGVSWGLR Molecular Formula: C96H142N26O22 Molecular Weight: 2012.3492 g/mol PE-22-28 Sequence: GVSWGLR Molecular Formula: C35H55N11O9 Molecular Weight: 773.8947 g/mol

PE-22-28 Research

What Is TREK-1?

The receptor that spadin and thus PE-22-28 primarily bind to is TREK-1. TREK-1 is a two-pore potassium channel regulated by a number of different molecules. It belongs to a large family of two-pore potassium channels that are important in regulating the excitability of neurons. TREK-1, in particular, is found in regions of the brain controlling mood, memory, and learning. These areas include the prefrontal cortex, the amygdala, and the hippocampus. Stimulating TREK-1 activity reduces excitability of the neuron while reducing TREK-1 function increases excitability and increases the likelihood of a depolarization event[3]. By reducing excitability of the neuron, TREK-1 can help to protect against excitotoxicity.

Depression

Research in mouse models of depression indicates that PE-22-28 is more effective in reversing the symptoms of depression than any currently used treatment and that it does so with fewer side effects. In fact, PE-22-28 has been shown to relieve depression in just 4 days without producing any side effects on other functions that are controlled by the TREK-1 channel.

There is strong evidence to show that the hippocampus is smaller (of reduced volume) in patients suffering from depressive disorder and other affect disorders. Additionally, research has shown that long-term administration of classic antidepressants (5-HT or norepinephrine selective reuptake inhibitors) boosts neurogenesis in the adult rodent hippocampus and leads to increased hippocampus volume[4]. The ability of PE-22-28 to reverse this loss of volume by stimulating neurogenesis indicates that it is fighting depression at its source and that it may help to uncover some of the underlying physiologic pathways that are deficient in the setting of depression[5].

The lack of side effects caused by spadin and PE-22-28 is just as important as the effects of these peptides. Current treatments for depression have a host of known side effects ranging from suicidality to changes in libido and problems with cognition. In fact, side effects are the number one reason that people stop using their antidepressants and are reluctant to return to them even after their depression worsens. Even ketamine, which has been newly touted as a potential rapid-onset treatment for depression has a host of side effects including delirium, hallucinations, muscle tremors, high blood pressure, and increased heart rate. So, despite its rapid onset of action, doctors have been reluctant to use ketamine in the treatment of depression because of the range and severity of its side effects[6].

There was initial concern that spadin would also cause a host of side effects because the TREK-1 receptor has been implicated in pain sensitivity, seizure activity, and cardiac ischemia. There was also concern that spadin and PE-22-28 may inhibit currents in TREK-2, TRAAK, TASK, and TRESK channels leading additional side effects. Research in mice, however, shows that none of these side effects are observed and, in fact, PE-22-28 has one of the smallest side effect profiles of any existing or experimental treatment for depression[7].

Post-Stroke Depression

Post-stroke depression (PSD) is a common condition following brain ischemia and is particularly refractory to standard treatment. Recent research has shown that TREK-1 over-expression likely plays a causative role in this condition. In experimental mouse models, this upregulation can be suppressed or reversed using both SSRI antidepressants as well as TREK-1 blockers like spadin[3]. Of course, the SSRIs take much longer to act and have a host of side effects. This suggests that PE-22-28 may prove effective in future trials exploring the treatment of PSD.

Neurogenesis

The ability of antidepressant drugs to upregulate neurogenesis in the hippocampus has been well-established. Research with PE-22-28 shows that this peptide can perform the same function, but in a shorter duration of time. Studies in mice show that PE-22-28 increases both neurogenesis and synaptogenesis after just four days. Preliminary results indicate that PE-22-28 roughly doubles the amount of BrdU (an exogenous marker that is incorporated into DNA and used to detect replication) positive cells in the hippocampus.  In the case of synaptogenesis, PE-22-28 appears to double the rate of synapse formation[2], [8].

Another clue that PE-22-28 is boosting cell division in the brain is the increase in CREB seen after its administration. CREB (cAMP response element-binding protein) is a transcription factor associated with neuronal plasticity, memory formation, and the development of spatial memory. CREB appears to be a necessary component in not just the growth of neurons, but in their protection as well. Research in Alzheimer’s disease has shown a down-regulation of CREB and scientists have long sought a drug capable of boosting CREB as a means of treating Alzheimer’s[9], [10]. PE-22-28 is being actively investigated for its ability to both prevent and reverse the symptoms of Alzheimer’s disease.

The hippocampus, while playing an important role in depression, is also a critical structure for learning and memory. It is a very plastic structure that research has revealed to be vulnerable to damage by a variety of insults. The hippocampus has been implicated in diseases ranging from depression to anxiety to Alzheimer’s disease. Improving its ability to regenerate following injury could help to treat a number of diseases. Notably, the role of the hippocampus in learning, memory, and spatial navigation suggests that PE-22-28 or a similar TREK-1 antagonist may prove to be an effective nootropic.

Now, it has generally been demonstrated in animal models that removing the TREK-1 channel is a recipe for disaster. In previous mouse models, knockout of TREK-1 increased significantly the likelihood of seizure activity and reduced the normal ability of this two-pore potassium channel to protect neurons from excitotoxicity. It came as a bit of surprise then that neither spadin nor PE-22-28 enhanced seizure activity. Even more interesting is the fact that mice treated with spadin are more resistant to developing generalized seizures[3]. PE-22-28 has even more profound protective effects than spadin.

Muscle Function

There is some research to suggest that TREK-1 plays an important role in the ability of muscle 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. While this particular aspect of the TREK-1 channel is still in the early stages of investigation, it is becoming increasingly important. There is hope that understanding the role of molecules like PE-22-28 in muscle contraction and relaxation may not only provide new treatment modalities for conditions like myogenic bladder dysfunction, but may also open up new pathways for understanding the physiology of muscle performance[11].

Summary

According to Dr. Jean Mazella, one of the lead researchers in the development of PE-22-28, the peptide was specifically designed to move forward the use of spadin analogs in clinics. PE-22-28 appears to be an effective treatment for depression and a potent stimulator of neurogenesis and synaptogenesis in the hippocampus. It has far fewer side effects than existing antidepressant medications and appears to retain much of its ability to antagonize TREK-1 even after modifications that boost half-life or alter the route of administration. In short, PE-22-28 appears to offer a strong target for guiding the development of a new generation of antidepressants and is helping to shed light on the burgeoning field of nootropics. It is also helping to expand the arsenal of drugs used to treat neurodegenerative diseases like Alzheimer’s disease.

Article Author

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.

THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused, or mislabeled as a drug, food, or cosmetic.

PE-22-28 is a synthetic peptide derived from the naturally occurring neuropeptide spadin, a sortilin-derived peptide known for its interaction with the TREK-1 (TWIK-related potassium channel-1) receptor. Researchers investigate PE-22-28 because it exhibits enhanced stability, improved TREK-1 antagonism, and greater experimental activity compared with native spadin.

As interest in neuroscience, neuroplasticity, neurogenesis, and ion-channel biology continues to grow, researchers frequently compare PE-22-28 suppliers based on purity, analytical testing, manufacturing quality, pricing, and supplier transparency.

This PE-22-28 Vendor Price Comparison Guide helps researchers evaluate suppliers using objective criteria including:

• Product Pricing

• Cost Per Milligram

• Product Purity

• Third-Party Testing

• Certificate of Analysis (COA)

• Vendor Reputation

• Customer Reviews

• Shipping Performance

• Product Availability

• Overall Value

Whether you're searching for the lowest-priced PE-22-28 supplier, the highest-purity research-grade material, or vendors with extensive laboratory verification, this guide provides a framework for comparing peptide suppliers.

Explore PE-22-28 Vendors by Criteria

Most Popular PE-22-28 Vendors

Compare suppliers frequently selected by neuroscience and ion-channel researchers.

Highest Reviewed PE-22-28 Vendors

Discover peptide suppliers with strong customer satisfaction and positive marketplace reputations.

Lowest Price PE-22-28 Vendors

Identify suppliers offering competitive pricing and favorable cost-per-milligram value.

Highest Purity PE-22-28 Vendors

Review suppliers providing transparent purity verification and analytical testing.

Best Value PE-22-28 Vendors

Compare pricing, testing documentation, customer support, and product quality.

Fastest Shipping PE-22-28 Vendors

Evaluate shipping reliability, packaging quality, and fulfillment performance.

Newly Listed PE-22-28 Vendors

Explore recently added suppliers offering PE-22-28 research peptides.

What Is PE-22-28?

Overview

PE-22-28 is a synthetic analog of spadin developed to improve the characteristics of the parent peptide while preserving its ability to antagonize the TREK-1 potassium channel.

Researchers investigate PE-22-28 because of its relationship with:

• TREK-1 signaling

• Neurogenesis

• Synaptogenesis

• Neuroplasticity

• Ion-channel biology

• Learning and memory research

• Neurodegenerative pathways

• Mood-regulation mechanisms

PE-22-28 has become an important experimental tool for studying neuronal excitability and neural-network adaptation.

Molecular Characteristics

PE-22-28 Information

Researchers evaluating PE-22-28 products should carefully review analytical documentation and molecular specifications.

Peptide Name

PE-22-28

Parent Peptide

Spadin

PE-22-28 Sequence

GVSWGLR

Molecular Formula

C35H55N11O9

Molecular Weight

773.8947 g/mol

Classification

Synthetic Spadin Analog

Biological Target

TREK-1 (TWIK-Related Potassium Channel-1)

Research Category

Neuroscience & Neuroplasticity Research

Spadin vs PE-22-28

Researchers often compare PE-22-28 with its parent peptide, spadin.

Spadin

Sequence

YAPLPRWSGPIGVSWGLR

Molecular Formula

C96H142N26O22

Molecular Weight

2012.3492 g/mol

Characteristics

• Naturally occurring

• Derived from sortilin

• TREK-1 antagonist

• Neurogenic activity

PE-22-28

Sequence

GVSWGLR

Characteristics

• Synthetic derivative of spadin

• Increased stability

• Smaller peptide structure

• Enhanced TREK-1 inhibition

• Improved experimental activity

Researchers frequently use PE-22-28 as a representative compound within the family of optimized spadin analogs.

Why Researchers Compare PE-22-28 Vendors

Research reproducibility depends heavily on peptide quality and manufacturing consistency.

Differences among suppliers may include:

• Product purity

• Batch consistency

• Stability testing

• Manufacturing standards

• Analytical verification

• Product documentation

• Storage procedures

• Quality-control systems

Careful supplier selection helps improve consistency and reliability across research projects.

How We Compare PE-22-28 Vendors

Third-Party Laboratory Testing

Independent laboratory testing remains one of the strongest indicators of peptide quality.

Researchers should prioritize suppliers offering:

• Third-party testing

• Purity verification

• Identity confirmation

• Batch-specific reports

Certificate of Analysis (COA)

A quality COA should contain:

• Batch number

• Testing date

• Purity percentage

• Identity verification

• Analytical methodology

Product Purity

Purity remains one of the most important factors when evaluating research peptides.

Higher-purity products generally contribute to improved reproducibility and experimental consistency.

Cost Per Milligram

Comparing product prices alone may not accurately reflect value.

Cost Per Milligram Formula

Product Price ÷ Total Milligrams = Cost Per Milligram

This metric provides a more accurate vendor comparison.

Customer Reviews

Customer experiences often provide insight regarding:

• Product consistency

• Packaging quality

• Shipping reliability

• Customer support

• Purchasing experience

Vendor Reputation

Established peptide suppliers often demonstrate:

• Transparent laboratory testing

• Reliable quality-control standards

• Consistent product availability

• Positive customer satisfaction

Current Research & Evidence

TREK-1 Research

The primary focus of PE-22-28 research involves TREK-1 potassium-channel biology.

Researchers continue investigating:

• Neuronal excitability

• Ion-channel regulation

• Potassium-channel signaling

• Synaptic communication

• Neural-network activity

This remains the central area of PE-22-28 research.

What Is TREK-1?

TREK-1 is a member of the two-pore potassium channel family.

Researchers investigate TREK-1 because of its involvement in:

• Neuronal excitability

• Synaptic signaling

• Memory formation

• Learning mechanisms

• Mood regulation

• Neuroprotection

TREK-1 is expressed in several regions of the brain, including:

• Hippocampus

• Amygdala

• Prefrontal cortex

These structures play important roles in cognitive and behavioral neuroscience research.

Key Areas of PE-22-28 Research

Neurogenesis Research

One of the most prominent areas of PE-22-28 investigation involves neurogenesis.

Researchers continue studying pathways associated with:

• Neuronal development

• Neural stem-cell activity

• Cellular differentiation

• Brain plasticity

• Neural regeneration

Additional research remains ongoing.

Synaptogenesis Research

Research has investigated PE-22-28 because of its relationship with:

• Synapse formation

• Neural connectivity

• Cellular communication

• Neural-network remodeling

• Synaptic plasticity

These pathways remain central to understanding brain adaptability.

Neuroplasticity Research

Scientists continue studying PE-22-28 because of its involvement in:

• Structural plasticity

• Functional plasticity

• Learning-associated adaptations

• Memory-related pathways

• Neural resilience

This remains a major area of neuroscience research.

Learning & Memory Research

Researchers investigate pathways involving:

• Hippocampal function

• Spatial memory

• Learning mechanisms

• Cognitive adaptation

• Memory consolidation

The hippocampus remains one of the most extensively studied structures in this field.

CREB Signaling Research

PE-22-28 has generated interest because of findings involving:

• CREB activation

• Neuronal plasticity

• Memory formation pathways

• Cellular adaptation

• Neuroprotective signaling

Research remains ongoing in this area.

Neurodegenerative Disease Research

Scientists continue evaluating pathways associated with:

• Cognitive decline

• Neuronal protection

• Synaptic preservation

• Brain aging

• Neurodegenerative mechanisms

Further investigations remain necessary.

Post-Stroke Research

Experimental studies continue examining:

• Neural recovery pathways

• Neuroplasticity mechanisms

• Neural adaptation processes

• Brain-repair signaling

Additional preclinical research remains ongoing.

Muscle Function Research

TREK-1 channels are also expressed outside the nervous system.

Researchers investigate:

• Muscle contractility

• Mechanical signaling

• Smooth-muscle responses

• Neuromuscular physiology

This remains an emerging field of investigation.

Why Researchers Study PE-22-28

PE-22-28 remains one of the more interesting neuroscience peptides because it spans multiple scientific disciplines.

Common research applications include:

• Neuroscience

• Neuroplasticity

• Ion-channel biology

• Learning and memory research

• Neurogenesis

• Synaptogenesis

• Neurodegenerative disease research

• Neuroprotection

Its ability to target TREK-1 signaling continues to attract significant scientific interest.

Research Limitations

Most findings involving PE-22-28 originate from:

• Cell-culture studies

• Animal models

• Laboratory investigations

• Preclinical neuroscience research

Additional studies remain necessary to fully characterize biological mechanisms and long-term effects.

Research findings should not be interpreted as evidence of approved therapeutic applications.

Product Quality & Analytical Testing

Why Testing Matters

Research-grade PE-22-28 products should undergo testing to verify:

• Identity

• Purity

• Stability

• Composition

• Batch consistency

Common Testing Methods

High-Performance Liquid Chromatography (HPLC)

Used to evaluate peptide purity and identify impurities.

Mass Spectrometry (MS)

Used to verify molecular mass and peptide identity.

Peptide Mapping

Assesses sequence and structural characteristics.

Batch Consistency Testing

Measures reproducibility across production lots.

Stability Analysis

Evaluates peptide integrity under storage conditions.

Identity Verification Testing

Confirms peptide authenticity.

Understanding PE-22-28 Pricing

Several factors influence pricing among peptide suppliers.

Product Purity

Higher-purity peptides often command premium pricing.

Specialized Synthesis

PE-22-28 is a niche neuroscience peptide with limited commercial production.

Analytical Verification

Comprehensive testing programs improve transparency while increasing production costs.

Research Demand

Growing interest in neuroplasticity and ion-channel biology contributes to demand.

Vendor Reputation

Trusted peptide suppliers frequently charge more due to established quality-assurance systems.

PE-22-28 Vendor Evaluation Checklist

Quality Verification

✅ Third-party testing available

✅ Certificate of Analysis provided

✅ Identity verification documented

✅ Purity information disclosed

✅ Batch-specific testing available

✅ Molecular verification provided

Vendor Reliability

✅ Positive customer reviews

✅ Transparent company information

✅ Responsive customer support

✅ Reliable inventory availability

Purchasing Experience

✅ Secure checkout process

✅ Shipment tracking available

✅ Clear return policies

✅ Reliable order fulfillment

Red Flags When Comparing Vendors

Testing Concerns

❌ No third-party testing

❌ Missing COAs

❌ Unverified purity claims

❌ Missing identity verification

❌ Outdated laboratory reports

Transparency Issues

❌ Missing sequence information

❌ No batch documentation

❌ Limited analytical data

❌ No supplier contact information

Service Problems

❌ Frequent inventory shortages

❌ Poor communication

❌ Negative customer reviews

❌ Unclear shipping policies

Frequently Asked Questions

What is PE-22-28?

PE-22-28 is a synthetic peptide derived from spadin and studied primarily as a TREK-1 potassium-channel antagonist in neuroscience research.

What is PE-22-28 used for in research?

Researchers investigate PE-22-28 in studies involving TREK-1 signaling, neurogenesis, synaptogenesis, neuroplasticity, learning and memory, neuronal excitability, and neurodegenerative pathways.

What is TREK-1?

TREK-1 is a two-pore potassium channel involved in regulating neuronal excitability, synaptic activity, neuroprotection, and several neural signaling pathways.

How is PE-22-28 different from spadin?

PE-22-28 is a shorter synthetic derivative of spadin that demonstrates improved stability and enhanced TREK-1 antagonism in experimental research models.

What should researchers review before purchasing?

Researchers should review:

• Certificate of Analysis (COA)

• HPLC purity testing

• Mass spectrometry verification

• Identity confirmation

• Vendor reputation

• Customer reviews

Why is third-party testing important?

Independent laboratory testing helps verify peptide identity, purity, and batch consistency while improving transparency and reproducibility.

Is the lowest-priced supplier always the best option?

No. Product quality, testing standards, supplier reliability, and analytical documentation are often more important than price alone.

Final Thoughts

PE-22-28 remains one of the most intriguing experimental neuroscience peptides because of its relationship with TREK-1 signaling, neurogenesis, synaptogenesis, neural plasticity, and ion-channel biology. Ongoing investigations continue exploring its usefulness as a research tool for understanding neuronal adaptation, memory formation, cognitive pathways, and neurodegenerative mechanisms.

When comparing PE-22-28 vendors, researchers should prioritize purity verification, third-party analytical testing, Certificate of Analysis availability, supplier reputation, and overall value rather than focusing solely on price. A structured vendor-comparison process can help identify suppliers capable of meeting rigorous research-quality standards.