Cortagen

Cortagen is a synthetic tetrapeptide (Alanine-Glutamic acid-Aspartic acid-Proline) identified as the active regulatory peptide within Cortexin, a polypeptide preparation extracted from bovine cerebral cortex. Cortexin itself is an approved pharmaceutical in Russia, widely used for stroke recovery, traumatic brain injury, and cognitive disorders. Cortagen was developed by the Khavinson group as the synthetic, defined-sequence bioregulator responsible for Cortexin's primary neuroprotective and neuroregulatory effects. The tetrapeptide is proposed to target cortical neurons and glial cells, modulating gene expression involved in synaptic plasticity, neurotransmitter metabolism, anti-apoptotic signaling, and neuroinflammation. Research suggests Cortagen improves cortical function in models of ischemic brain injury, aging-related cognitive decline, and neurodegenerative conditions. It is frequently used alongside Pinealon and Epitalon in thorough brain anti-aging protocols.

Cortagen is proposed to penetrate cell and nuclear membranes in cortical tissue, interacting with DNA sequences that regulate genes involved in synaptic function, neuronal survival, and neurotransmitter metabolism. Research shows it upregulates expression of neurotrophic factors (BDNF, NGF) in cortical neurons, enhances GABAergic and glutamatergic neurotransmission balance, and activates anti-apoptotic pathways (Bcl-2/Bax ratio). In ischemic models, Cortagen reduces excitotoxic damage by modulating NMDA receptor-mediated calcium influx and enhancing endogenous antioxidant defenses. The peptide also reduces neuroinflammation through NF-κB modulation in microglia, shifting them from neurotoxic to neuroprotective phenotypes. Its cortex-specific targeting is proposed to result from preferential DNA-binding in neurons expressing cortex-specific transcription factors.