Cortagen

Cortagen is a synthetic bioregulator designed to mimic peptides found in the cerebral cortex. It supports both the nervous and cardiovascular systems through mechanisms that promote gene expression, reduce oxidative stress, enhance neural repair, and regulate inflammatory pathways. Cortagen (Ala–Glu–Asp–Pro) replicates regulatory functions of endogenous cortical peptides (Cytogen family). It exerts neuroprotective and cardioregulatory effects by modulating gene expression, epigenetic architecture, and cellular repair pathways. Benefits include improved cognitive performance, accelerated peripheral nerve recovery, reduced neuroinflammation, and reprogramming of cardiac gene expression following injury or oxidative stress.

- Enhance cognitive function and memory retention

- Support cardiovascular gene expression and cardiac recovery

- Manage age-related neurological decline or inflammatory brain conditions

- Assist with neuroregeneration or oxidative stress resilience

Mechanism of Action

How this peptide works in the body

DNA Binding and Epigenetic Modulation

Cortagen enters the nucleus of neurons and cardiomyocytes where it binds to specific AT-rich motifs within heterochromatin domains. This binding recruits histone acetyltransferases (HATs), which acetylate histones H3 and H4, leading to chromatin decondensation. This epigenetic shift increases transcriptional access to previously silenced genes involved in neurotrophin synthesis (e.g., BDNF), cardiac stress-resistance proteins, and DNA repair enzymes. In aged or post-ischemic tissue, this reactivation of transcription contributes to structural and functional recovery.

Transcription Factor Modulation

Cortagen enhances the activity of transcription factors including CREB (cAMP response element-binding protein), MEF2 (myocyte enhancer factor 2), and FOXO1 in both neural and cardiac tissues. These factors drive the expression of key genes involved in neurogenesis, mitochondrial function, and synaptic plasticity. Concurrently, Cortagen suppresses pro-inflammatory regulators such as NF-κB and AP-1, reducing expression of IL-6, TNF-α, and other catabolic cytokines, thereby promoting a regenerative and anti-inflammatory cellular phenotype.

Neuron Membrane Regulation

Electrophysiological studies show that Cortagen hyperpolarizes neuronal membranes by increasing potassium conductance through inwardly rectifying K⁺ channels (e.g., GIRK2), stabilizing resting potential and reducing spontaneous action potential firing. This reduces calcium influx and excitotoxicity, preserving neuron viability during ischemic stress or traumatic injury.

Neurotrophic Factor Induction

Cortagen upregulates the transcription and translation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which act via TrkB and TrkA receptors to activate PI3K/Akt and MAPK/ERK signaling pathways. These cascades promote neuronal survival, axonal growth, and long-term potentiation (LTP), key for cognitive repair and plasticity.

Peripheral Nerve Regeneration

In models of sciatic nerve injury, Cortagen stimulates Schwann cell proliferation and migration via upregulation of neuregulin-1 and NGF, initiating Wallerian degeneration clearance and axon remyelination. Although it does not enhance compound action potential conduction at later stages, its early-phase effects increase GAP-43 and βIII-tubulin expression, markers of axonal sprouting.

Cardiac Gene Expression Regulation

Cortagen modulates transcription in cardiomyocytes through GATA4 and MEF2C activation, increasing expression of structural proteins (e.g., α-actinin, desmin), mitochondrial enzymes (e.g., cytochrome c oxidase), and stress-adaptive genes (e.g., HSP70). These effects support contractile integrity and reduce apoptosis in post-infarct and aging myocardium.

Oxidative Stress and Antioxidant Defense

Cortagen activates the Nrf2/ARE (antioxidant response element) pathway in both neural and cardiac cells, increasing transcription of endogenous antioxidant enzymes including heme oxygenase-1 (HO-1), superoxide dismutase 2 (SOD2), and glutathione peroxidase (GPx). This reduces lipid peroxidation, protein carbonylation, and mitochondrial DNA damage, preserving cellular energy output and redox balance.

Anti-Inflammatory Cytokine Rebalancing

Cortagen suppresses expression of IL-1β, IL-6, and TNF-α through inhibition of IκB kinase (IKK) activation, which blocks NF-κB nuclear translocation. Simultaneously, it promotes secretion of IL-10 and TGF-β by glial cells and macrophage-derived suppressor cells (MDSCs), facilitating resolution of neuroinflammation and preserving the blood-brain barrier.