Overview
Overview
Cortagen dosage protocols are designed around this synthetic tetrapeptide (Ala-Glu-Asp-Pro) that belongs to the Khavinson bioregulator class, studied for its neuroprotective and neuroregenerative properties[1][2]. Research indicates Cortagen may support peripheral nerve regeneration, enhance cognitive function, reduce oxidative stress in neural tissues, and promote cellular repair mechanisms without significant adverse effects at therapeutic doses[3][4]. This educational protocol presents a once
- Category
- Longevity
- Routes
- subcutaneous
Mechanism
Cortagen
Mechanism of action
Mechanism of action
Cortagen (Ala-Glu-Asp-Pro) is a synthetic tetrapeptide derived from amino acid analysis of the natural brain cortex preparation Cortexin [3] . It acts as a gene expression modulator and epigenetic regulator, influencing the synthesis of proteins involved in neuronal growth, differentiation, and stress resistance [6] [7] . Preclinical studies demonstrate that Cortagen can upregulate neurotrophic factors, reduce oxidative stress markers, and accelerate peripheral nerve regeneration—increasing nerve fiber growth rate and conduction velocity by 27–40% in injury models [1] . In chronic cerebral ischemia models, Cortagen improved behavioral recovery and protected against oxidative damage [2] .
Key research findings
- 01
Animal model (rat): In sciatic-nerve transection/suture models, intramuscular Cortagen (research-reported at 10 ug/kg for 10 days) increased regenerating nerve-fiber growth rate by ~27% and conduction velocity by ~40%, with a separate report describing a delayed effect on restoration of injured-nerve function (Turchaninova et al., 2000, Bull Exp Biol Med, PMID 11276314; Kolosova et al., 2002, Dokl Biol Sci, DOI 10.1023/a:1016098302564). Rodent observations only; not established in humans.
- 02
Animal model (rat): Cortagen injections reduced lipid-peroxidation products and oxidative protein modification in serum and cerebral cortex (Kozina, 2007, Bull Exp Biol Med, DOI 10.1007/s10517-007-0230-8) and, in chronic cerebral-ischemia models, were associated with faster recovery of behavior and limited oxidative stress (Zarubina & Shabanov, 2011, Eksp Klin Farmakol, PMID 21476278; 2016, DOI 10.1007/s10517-016-3193-9). These are preclinical antioxidant-associated signals, not clinical evidence.
- 03
Animal model (mouse): A cDNA microarray of >15,000 transcripts found that a 5-day Cortagen course altered expression of ~110 genes in mouse heart, and separate in-vivo work showed modulation of hypothalamic IL-2 mRNA, supporting a gene-expression-modulating mechanism shared in part with related short peptides (Anisimov SV, Khavinson, Anisimov VN, 2004, Neuro Endocrinol Lett, PMID 15159690; Kazakova et al., 2005, Bull Exp Biol Med, DOI 10.1007/s10517-005-0388-x).
- 04
In vitro (rat organotypic culture): Cortagen showed tissue-specific stimulation of cerebral-cortex explant growth, the basis of the 'cytogen' tissue-specificity hypothesis, and activated IL-2 mRNA in cultured splenocytes more weakly than related peptides (Khavinson, 2001, Bull Exp Biol Med, DOI 10.1023/a:1013058701974; Kazakova et al., 2002, Bull Exp Biol Med, DOI 10.1023/a:1020210615148).
- 05
In vitro (ex vivo human lymphocytes, donors aged 75-88): Cortagen, alongside other short peptides, was reported to activate ribosomal genes and decondense age-condensed chromatin (deheterochromatinization), an epigenetic-aging readout in cultured cells, not a clinical outcome (Khavinson, Lezhava & Malinin, 2004, Bull Exp Biol Med, DOI 10.1023/b:bebm.0000024393.40560.05; Lezhava et al., 2023, Georgian Med News, PMID 37042594).
- 06
In vitro + animal model (null/weak results, included for balance): Cortagen produced no comitogenic effect on mouse thymocyte proliferation (Khavinson et al., 2002, Bull Exp Biol Med, DOI 10.1023/a:1019830308824) and, unlike the related peptide epithalon, did not alter immunity or hemostasis parameters in hypophysectomized or aged birds (Kuznik et al., 2008, Adv Gerontol, PMID 19432169); observed effects in research appear tissue- and context-dependent.
Primary source: Based on PubMed-indexed literature, the research base for Cortagen (synthetic tetrapeptide Ala-Glu-Asp-Pro) is real but narrow and preclinical: roughly 15 indexed reports, overwhelmingly from a single Russian research lineage (Khavinson / St. Petersburg Institute of Bioregulation and Gerontology and collaborators), concentrated in Bulletin of Experimental Biology and Medicine and based mainly on rodent and in vitro/ex vivo models, with several reports in Russian and some null findings. No registered or controlled human efficacy trials were located and independent replication outside the originating group is limited, so research maturity remains low.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Supports peripheral nerve regeneration with improved growth rate and conduction velocity in injury models[1].
Demonstrates neuroprotective effects in ischemia models by reducing lipid peroxidation and preserving antioxidant enzyme activity[2].
May enhance cognitive function and memory through promotion of synaptic plasticity and neurite outgrowth[4][5].
Shows gene expression modulation in cardiac and neural tissues with broad regulatory effects[3][6].
Protocol Reference
Protocol reference
Commonly cited research range: 1–2 mg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Weeks 1–2
1000 mcg
Weeks 3–4
2000 mcg
| Phase | Reference amount | Units / volume |
|---|---|---|
| Weeks 1–2 | 1000 mcg | 15 units (0.15 mL) |
| Weeks 3–4 | 2000 mcg | 30 units (0.30 mL) |
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️Draw 3.0 mL bacteriostatic water with a sterile syringe.
- 02🧴Inject slowly down the vial wall; avoid foaming.
- 03💉Gently swirl/roll until dissolved (do not shake).
- 04💧Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
- 05🔄Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
Store at −20 °C (−4 °F) for long-term; 2–8 °C (35.6–46.4 °F) acceptable for short-term (weeks to months).
Refrigerate at 2–8 °C (35.6–46.4 °F); use within 4 weeks and avoid freeze–thaw .
Allow vials to reach room temperature before opening to reduce condensation uptake.
Clinical Evidence
Clinical evidence
Preclinical research reports neuroregenerative and antioxidant activity; human data are limited.
Based on PubMed-indexed literature, the research base for Cortagen (synthetic tetrapeptide Ala-Glu-Asp-Pro) is real but narrow and preclinical: roughly 15 indexed reports, overwhelmingly from a single Russian research lineage (Khavinson / St. Petersburg Institute of Bioregulation and Gerontology and collaborators), concentrated in Bulletin of Experimental Biology and Medicine and based mainly on rodent and in vitro/ex vivo models, with several reports in Russian and some null findings. No registered or controlled human efficacy trials were located and independent replication outside the originating group is limited, so research maturity remains low.
- 01Animal model (rat): In sciatic-nerve transection/suture models, intramuscular Cortagen (research-reported at 10 ug/kg for 10 days) increased regenerating nerve-fiber growth rate by ~27% and conduction velocity by ~40%, with a separate report describing a delayed effect on restoration of injured-nerve function (Turchaninova et al., 2000, Bull Exp Biol Med, PMID 11276314; Kolosova et al., 2002, Dokl Biol Sci, DOI 10.1023/a:1016098302564). Rodent observations only; not established in humans.
- 02Animal model (rat): Cortagen injections reduced lipid-peroxidation products and oxidative protein modification in serum and cerebral cortex (Kozina, 2007, Bull Exp Biol Med, DOI 10.1007/s10517-007-0230-8) and, in chronic cerebral-ischemia models, were associated with faster recovery of behavior and limited oxidative stress (Zarubina & Shabanov, 2011, Eksp Klin Farmakol, PMID 21476278; 2016, DOI 10.1007/s10517-016-3193-9). These are preclinical antioxidant-associated signals, not clinical evidence.
- 03Animal model (mouse): A cDNA microarray of >15,000 transcripts found that a 5-day Cortagen course altered expression of ~110 genes in mouse heart, and separate in-vivo work showed modulation of hypothalamic IL-2 mRNA, supporting a gene-expression-modulating mechanism shared in part with related short peptides (Anisimov SV, Khavinson, Anisimov VN, 2004, Neuro Endocrinol Lett, PMID 15159690; Kazakova et al., 2005, Bull Exp Biol Med, DOI 10.1007/s10517-005-0388-x).
- 04In vitro (rat organotypic culture): Cortagen showed tissue-specific stimulation of cerebral-cortex explant growth, the basis of the 'cytogen' tissue-specificity hypothesis, and activated IL-2 mRNA in cultured splenocytes more weakly than related peptides (Khavinson, 2001, Bull Exp Biol Med, DOI 10.1023/a:1013058701974; Kazakova et al., 2002, Bull Exp Biol Med, DOI 10.1023/a:1020210615148).
- 05In vitro (ex vivo human lymphocytes, donors aged 75-88): Cortagen, alongside other short peptides, was reported to activate ribosomal genes and decondense age-condensed chromatin (deheterochromatinization), an epigenetic-aging readout in cultured cells, not a clinical outcome (Khavinson, Lezhava & Malinin, 2004, Bull Exp Biol Med, DOI 10.1023/b:bebm.0000024393.40560.05; Lezhava et al., 2023, Georgian Med News, PMID 37042594).
- 06In vitro + animal model (null/weak results, included for balance): Cortagen produced no comitogenic effect on mouse thymocyte proliferation (Khavinson et al., 2002, Bull Exp Biol Med, DOI 10.1023/a:1019830308824) and, unlike the related peptide epithalon, did not alter immunity or hemostasis parameters in hypophysectomized or aged birds (Kuznik et al., 2008, Adv Gerontol, PMID 19432169); observed effects in research appear tissue- and context-dependent.
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to Cortagen.
- 01PubMed — Effect of tetrapeptide cortagen on regeneration of sciatic nerve (nerve growth rate and conduction velocity improvements) View Source
- 02PubMed — Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia View Source
- 03PubMed (Neuroendocrinology Letters) — Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray View Source
- 04PubMed (Biogerontology) — Peptide bioregulation of aging: results and prospects (lifespan extension and biomarker modulation) View Source
- 05Bentham Open (Open Neuropsychopharmacology Journal) — Modulatory effects of Cortexin and Cortagen on locomotor activity and anxiety-related behavior in mice View Source
- 06MDPI (Molecules) — Peptide Regulation of Gene Expression: A Systematic Review (epigenetic mechanisms) View Source
- 07Springer (Bulletin of Experimental Biology and Medicine) — Mechanisms Underlying Geroprotective Effects of Peptides View Source
- 08MedlinePlus — Subcutaneous (SQ) injections: technique, site rotation, and best practices View Source
- 09CDC (Subcut Injection PDF) — Vaccine Administration: Subcutaneous (SUBCUT) Injection technique and guidance View Source
- 10Bachem — Handling and Storage Guidelines for Peptides (stability and storage conditions) View Source
- 11MDPI (International Journal of Molecular Sciences) — Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes View Source
- 12Wikipedia — Cortagen (tetrapeptide overview and background) View Source
- 13Pure Lab Peptides — Cortagen (20 mg) product page (quality and batch documentation) View Source
Observed Effects
Observed effects in cited research
Reported
- Generally well tolerated with no significant adverse effects observed at therapeutic doses in animal studies[5].
- Occasional mild injection-site reactions (redness/itch) may occur with subcutaneous administration.
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Current evidence is limited to in vitro and/or animal-model research; human data are minimal or absent. Consult a licensed healthcare professional for any clinical decisions.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| Cortagenthis | A synthetic tetrapeptide (Ala-Glu-Asp-Pro) of the Khavinson bioregulator class studied for neuroprotective and neuroregenerative activity, including peripheral nerve repair. | subcutaneous | Investigational / RUO |
| Epitalon (Epithalon) | A synthetic tetrapeptide (Ala-Glu-Asp-Gly) studied for activation of telomerase and modulation of pineal/melatonin and circadian pathways, of interest in geroprotection research. | subcutaneous | Investigational / RUO |
| FOXO4-DRI | A D-retro-inverso peptide designed to disrupt the FOXO4-p53 interaction in senescent cells, releasing p53 to selectively induce apoptosis of senescent cells (a senolytic mechanism). | subcutaneous | Investigational / RUO |
| Glutathione | An endogenous tripeptide (gamma-L-glutamyl-L-cysteinyl-glycine) functioning as a major intracellular antioxidant and redox buffer, supporting phase-II detoxification conjugation and neutralization of reactive oxygen species. | subcutaneous | Investigational / RUO |
| Livagen | A synthetic tetrapeptide bioregulator (Lys-Glu-Asp-Ala) studied for peptidase modulation and epigenetic/chromatin effects (e.g., heterochromatin decondensation) in aging cell models. | subcutaneous | Investigational / RUO |
| DSIP | A naturally occurring nonapeptide studied for influence on sleep architecture and hypothalamic-pituitary-adrenal (stress-axis) modulation; its precise receptor targets remain incompletely characterized. | subcutaneous | Investigational / RUO |
| GHK-Cu | Stimulates collagen and glycosaminoglycan synthesis, promotes angiogenesis, and acts as antioxidant and anti-inflammatory agent. | subcutaneous, topical | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro) produced by directed synthesis based on amino-acid analysis of the cerebral-cortex peptide extract Cortexin; it is one of the Russian 'short peptide bioregulators' (cytogens) studied in aging-related research (Anisimov SV et al., 2004, Neuro Endocrinol Lett, PMID 15159690). It is a research-use-only material, not a medicine.
Limited peer-reviewed data. The indexed literature is sparse (about 15 PubMed records), mostly in vitro and rodent studies originating largely from one research group, several published in Russian, and includes some null results. No registered or controlled human efficacy trials were located, so findings should be treated as early and preliminary.
In rat sciatic-nerve injury models, Cortagen was reported to increase regenerating-fiber growth rate and nerve conduction velocity, with a follow-up describing a delayed effect on restoration of injured-nerve function (Turchaninova et al., 2000, Bull Exp Biol Med, PMID 11276314; Kolosova et al., 2002, Dokl Biol Sci, DOI 10.1023/a:1016098302564). These are animal-model observations and do not establish effects in humans.
In rats, Cortagen reduced markers of lipid peroxidation and oxidative protein modification (Kozina, 2007, Bull Exp Biol Med, DOI 10.1007/s10517-007-0230-8), and in cultured lymphocytes from elderly donors it was associated with ribosomal-gene activation and chromatin decondensation (Khavinson, Lezhava & Malinin, 2004, Bull Exp Biol Med, DOI 10.1023/b:bebm.0000024393.40560.05). These are mechanistic, cell-level and animal-level research findings, not proof of a clinical anti-aging benefit.
Yes, and honest reporting matters. Cortagen showed no comitogenic effect on mouse thymocyte proliferation (Khavinson et al., 2002, Bull Exp Biol Med, DOI 10.1023/a:1019830308824) and, unlike the related peptide epithalon, did not change immunity or hemostasis measures in hypophysectomized or aged birds (Kuznik et al., 2008, Adv Gerontol, PMID 19432169). Observed effects in research appear tissue- and context-dependent rather than uniform.
This is research-use-only material and the following is not medical advice. Research-reported parameters come only from animal models (for example, 10 ug/kg intramuscular in rats; Turchaninova et al., 2000, PMID 11276314), research-reported ranges vary, and they do not translate to human dosing; refer to your study's protocol reference rather than any general guidance. Human dosing has not been established in the indexed literature.
Cautiously. Vendor and blog claims currently outrun the peer-reviewed record: the indexed studies are preclinical, partly null, and concentrated in one research lineage, and no controlled human efficacy trials were located. Strong human-benefit claims should be treated as unsupported by the current research evidence.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.