Cortagen
Cortagen is a synthetic tetrapeptide bioregulator (Ala-Glu-Asp-Pro) studied for its effects on central nervous system gene expression, chromatin remodeling, and neuroprotective signaling in neural tissues.
Cortagen is a synthetic tetrapeptide bioregulator with the sequence Ala-Glu-Asp-Pro (AEDP), belonging to the Khavinson class of short regulatory peptides designed to exhibit tissue-preferential gene-expression modulation. Developed at the Saint Petersburg Institute of Bioregulation and Gerontology, Cortagen demonstrates primary activity in central nervous system models, where it has been investigated for effects on peripheral nerve regeneration, chromatin remodeling, oxidative stress regulation, and cytokine signaling.
Mechanism of Action
Cortagen operates through the bioregulatory peptide framework described by Khavinson (2004), in which short peptides modulate gene expression by interacting with chromatin structure and DNA promoter regions rather than through classical receptor-ligand pharmacology.
Chromatin Remodeling: Lezhava et al. (2006) demonstrated that Cortagen and related bioregulatory peptides induce reactivation of heterochromatin in lymphocytes from elderly subjects. The peptide promotes decondensation of constitutive heterochromatin regions, restoring chromatin accessibility patterns toward those observed in younger cells. This chromatin-level activity is proposed as the upstream mechanism through which Cortagen influences downstream gene expression across multiple targets.
Gene Expression Modulation: Anisimov et al. (2004) used microarray analysis to characterize Cortagen's effects on gene expression in mouse heart tissue, identifying differential expression across genes involved in cellular stress responses, apoptosis regulation, signal transduction, and tissue repair. The multi-gene expression profile is consistent with a systems-level transcriptional modulator rather than a single-target pharmacological agent.
Oxidative Stress Regulation: Kozina (2007) evaluated Cortagen's effects on free-radical processes, demonstrating modulation of lipid peroxidation products and antioxidant enzyme activity in experimental models. The peptide shifted oxidative balance markers toward reduced oxidative stress, suggesting neuroprotective activity in tissues with high metabolic oxygen demand.
Immune Signaling: Kazakova et al. (2002) showed that Cortagen modulates interleukin-2 gene expression in splenocyte cultures in vitro, indicating a role in cytokine-mediated immune regulation. This immunomodulatory dimension complements the peptide's primary neuroactive profile.
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Cortagen
**Cortagen** is a synthetic tetrapeptide bioregulator with the sequence Ala-Glu-
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Research
Peripheral Nerve Regeneration
Turchaninova et al. (2000) investigated Cortagen's effects on sciatic nerve regeneration in a rat transection model. Animals treated with Cortagen showed improved histological and morphometric indicators of nerve repair compared to controls, including enhanced axonal regrowth and myelination parameters. This study established Cortagen's primary identity as a neuro-active bioregulator with tissue-repair-promoting properties in peripheral nerve injury models.
Chromatin Reactivation in Aging
Khavinson et al. (2004) examined the effects of short peptides including Cortagen on lymphocyte chromatin structure in elderly subjects. The peptide induced measurable changes in chromatin condensation state, with heterochromatin regions showing increased accessibility. This finding was extended by Lezhava et al. (2006), who demonstrated that anti-aging peptide bioregulators including Cortagen can reactivate silenced chromatin regions in senescent cells, suggesting a mechanism for restoring age-diminished gene expression capacity.
Gene Expression Profiling
Anisimov et al. (2004) conducted microarray-based transcriptomic analysis of mouse heart tissue following Cortagen administration. The study identified altered expression in gene clusters associated with apoptotic regulation, stress response signaling, ion channel function, and extracellular matrix maintenance. The broad expression changes across functionally diverse gene families support the hypothesis that Cortagen operates at the chromatin-accessibility level rather than through a single receptor pathway.
Free Radical and Oxidative Balance
Kozina (2007) evaluated bioactive tetrapeptides including Cortagen for their effects on free-radical processes in experimental systems. Cortagen treatment was associated with reduced lipid peroxidation products and modulated antioxidant enzyme activity, indicating a shift in redox balance toward reduced oxidative damage. These findings are relevant to neuroprotection given the high susceptibility of neural tissues to oxidative injury.
Interleukin-2 Gene Expression
Kazakova et al. (2002) demonstrated that Cortagen modulates IL-2 gene expression in vitro using mouse splenocyte preparations. IL-2 is a critical cytokine for T-cell proliferation and differentiation, and its regulation by a tetrapeptide bioregulator suggests intersection between Cortagen's chromatin-remodeling mechanism and functional immune output. This finding positions Cortagen at the interface of neuroimmune regulation.
Safety Profile
Cortagen has been evaluated in preclinical rodent studies with no significant adverse effects reported at experimental doses. As a short tetrapeptide composed of natural amino acids (Ala-Glu-Asp-Pro), it is expected to undergo rapid enzymatic degradation to constituent amino acids. The limited clinical data available derives primarily from Russian bioregulatory peptide research programs. No controlled human clinical trials with standardized safety endpoints have been published in Western peer-reviewed literature. The peptide's short sequence and natural amino acid composition suggest low immunogenicity risk, though formal toxicology studies meeting international regulatory standards have not been reported.
Pharmacokinetic Profile
- Half-life
- Minutes (short peptide); effects persist via epigenetic changes
Quick Start
- Typical Dose
- 10-20 mg daily
- Frequency
- Once daily for 10-20 consecutive days
- Route
- Subcutaneous injection
- Cycle Length
- 10-20 days per cycle
- Storage
- Capsules: room temperature; Injectable lyophilized: 2-8°C; Reconstituted: 2-8°C refrigerated
Molecular Structure
- Formula
- C17H27N5O8
- Weight
- 416 Da
- Length
- 4 amino acids
- CAS
- Not established
- PubChem CID
- 18439621
- Exact Mass
- 430.1700 Da
- LogP
- -6.5
- TPSA
- 216 Ų
- H-Bond Donors
- 6
- H-Bond Acceptors
- 10
- Rotatable Bonds
- 11
- Complexity
- 711
Identifiers (SMILES, InChI)
InChI=1S/C17H26N4O9/c1-8(18)14(26)19-9(4-5-12(22)23)15(27)20-10(7-13(24)25)16(28)21-6-2-3-11(21)17(29)30/h8-11H,2-7,18H2,1H3,(H,19,26)(H,20,27)(H,22,23)(H,24,25)(H,29,30)/t8-,9-,10-,11-/m0/s1
PLTRIMAUDDQYRV-NAKRPEOUSA-NResearch Indications
Neurological Support
Shows beneficial long-term results in research following ischemic brain injury.
Research demonstrates effects on restoration of injured nerve function.
Regulates inflammatory response in the nervous system.
Immune Regulation
Helps regulate immune function by reducing autoimmune reactions.
Stimulates interleukin-2 expression for immune regulation.
Anti-Aging
Restores balance between pro- and anti-oxidative processes.
Addresses age-related CNS changes through bioregulation.
Research Protocols
oral
Available in capsule form for oral administration. Short peptides can be absorbed orally and reach target tissues. Typical protocol involves 10-20 day cycles, often repeated 2-3 times per year.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Standard protocol | 10-20 mg | Daily for 10-20 days | —(Route: Oral capsules) |
subcutaneous Injection
Brain bioregulator peptide. Short 4-week cycle with morning administration.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Loading phase | 1,000 mcg | Once daily (morning) | Weeks 1-2 |
| Full dose | 2,000 mcg | Once daily (morning) | Weeks 3-4(Cycle 4 weeks, extendable to 8) |
Reconstitution Guide (20mg vial + 3mL BAC water)
- Wipe vial tops with alcohol swab
- Draw 3.0 mL bacteriostatic water into syringe
- Inject slowly down the inside wall of the peptide vial
- Gently swirl to dissolve — never shake
- Resulting concentration: 6.67 mg/mL
- For 1,000 mcg (1 mg) dose: draw 15 units (0.15 mL)
- For 2,000 mcg (2 mg) dose: draw 30 units (0.30 mL)
- Store reconstituted vial refrigerated at 2-8°C
Interactions
Peptide Interactions
Complementary CNS bioregulators; Cortagen for cortex, Pinealon for general brain.
Often combined in comprehensive anti-aging Khavinson protocols.
Different organ targets; can be used in comprehensive bioregulator protocols.
Part of Khavinson bioregulator family; targets different tissue.
What to Expect
What to Expect
Gene expression modulation begins
Effects persist due to epigenetic changes
Neurological function improvements
Cumulative benefits with periodic cycles
Safety Profile
Common Side Effects
- Generally well-tolerated
- Minimal side effects reported
Contraindications
- Active neurological emergencies (seek medical care)
- Known hypersensitivity
- Pregnancy or breastfeeding
Discontinue If
- Allergic reactions
- Unusual neurological symptoms
Quality Indicators
What to look for
- White powder or capsules
- Clear solution if reconstituted
- Proper packaging and labeling
Caution
- Unknown source or purity
Red flags
- Discoloration
- Unusual odor
- Damaged packaging
Frequently Asked Questions
References (9)
- [7]Lezhava T et al Anti-aging peptide bioregulators induce reactivation of chromatin Georgian Med News (2006)
- [8]
- [4]Khavinson Peptide Bioregulators (2020)
- [9]Kazakova TB et al In vitro effect of short peptides on expression of interleukin-2 gene in splenocytes Bull Exp Biol Med (2002)
- [10]Khavinson VK et al Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium Molecules (2021)
- [6]Khavinson VK, Lezhava TA, Malinin VV Effects of short peptides on lymphocyte chromatin in senile subjects Bull Exp Biol Med (2004)
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