Cortagen

Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro) derived from brain cortex polypeptide extract Cortexin, developed by Vladimir Khavinson as part of the peptide bioregulator family. It demonstrates neuroprotective properties through epigenetic gene regulation, promotes nerve regeneration, and crosses the blood-brain barrier to exert direct CNS effects. Research shows it increases nerve fiber growth rate by 27% and conduction velocity by 40%, while modulating gene expression across 110+ genes involved in neural repair, cardiovascular function, and cellular differentiation.

Neuroprotection and Cognitive Function

Cortagen prevents excessive lipid peroxidation and maintains antioxidant activity in brain tissues during chronic ischemia ^[1][2]. It accelerates recovery of disturbed behavior in ischemic rats and demonstrates neuroprotective effects by stabilizing mitochondrial function and attenuating oxidative stress markers ^[1][2]. The peptide enhances motor stimulation without negative effects on emotional-affective profiles, suggesting potential benefits for treating depressive symptoms ^[3].

Nerve Regeneration

Intramuscular injection of 10 μg/kg cortagen for 10 days after sciatic nerve transection increased growth rate and conduction velocity in regenerating nerve fibers by 27% and 40%, respectively ^[4]. In humans, Cortagen demonstrated pronounced therapeutic effects on structural and functional posttraumatic recovery of peripheral nerve tissue ^[5]. The peptide stimulates neural growth in vitro, presumably through interaction with neurotrophic factors ^[3].

Gene Expression and Epigenetic Regulation

Cortagen modulates expression of 110+ known genes across various functional categories, affecting cardiac, neural, and immune tissue ^[5][6]. It induces deheterochromatinization (decondensation) of aged heterochromatin and activates ribosomal genes, with selective effects on specific chromosomal regions ^[7]. The peptide regulates gene expression by binding to promoter regions, making them inaccessible to DNA methyltransferases and resulting in gene activation ^[8][9].

Stem Cell Differentiation

Short peptides including AEDP promote neuronal differentiation of human periodontal ligament stem cells, increasing expression of GAP43 (neurotransmission) and Nestin (early neuronal precursors) ^[10][11]. These peptides interact with DNA and histone proteins, affecting template-directed synthesis, replication, transcription, and DNA repair ^[9].

Anti-Aging and Longevity

As part of the peptide bioregulator family, related compounds increased mean lifespan by 20-40% in animal models, slowed age-related biomarker changes, and suppressed spontaneous and chemically-induced tumorigenesis ^[12][13]. Peptide bioregulators stimulate proliferation and differentiation while suppressing apoptosis, leading to restoration of organ functions ^[12].

Cardiovascular Effects

Cortagen affects cardiovascular and cerebrovascular parameters in humans ^[5]. Gene expression analysis revealed modulation of genes including Pass1, Hsc70, Bmp2, Wnt4, Eps15, and Eps15-rs in cardiac tissue ^[5].

Safety Profile

Cortagen demonstrates excellent safety in preclinical research, with peptides active at very low dosages and no reported side effects ^[3]. Acute and sub-chronic administration led to motor stimulation without negative effects on emotional-affective profiles in animal studies ^[3].

Clinical Experience

In humans, Cortagen has been used for posttraumatic recovery of peripheral nerve tissue with positive therapeutic outcomes and no reported adverse effects ^[5]. The compound is authorized by the Russian Ministry of Health as part of the Cortexin preparation for correction of cerebral functions .

Dosing

Research dosages range from 0.01-0.10 mg/kg in animal studies, with 0.03 mg/kg showing optimal locomotor enhancement effects ^[3]. In rats, 10 μg/kg administered intramuscularly for 10 days demonstrated nerve regeneration benefits ^[4]. Human research applications suggest approximately 10 μg/kg body weight, with typical supplemental dosing at 2mg (20 units) daily ^[3].

Pharmacokinetics

Cortagen crosses the blood-brain barrier effectively due to its small molecular weight (430.41 Da) and specific tetrapeptide sequence . Like other short peptides, it likely has a short half-life requiring daily administration. The peptide can penetrate cell and nuclear membranes to interact directly with DNA and histones ^[8][9].

Contraindications and Precautions

No specific contraindications or serious adverse events have been reported in available research literature ^[3][12]. However, as an experimental compound not approved by FDA or EMA, it should only be used in research settings. Long-term safety data in humans remains limited despite decades of Russian clinical use.

Peptide Stability

As with other small peptides, Cortagen is subject to hydrolysis by amino- and carboxy-peptidases, which may affect bioavailability and necessitate specific formulation approaches for therapeutic applications.