Cortexin

Mechanism (as reported)

Research suggests multiple mechanisms for cortexin’s neuroprotective properties, including inhibition of the initiator protease caspase-8 in brain, and possible interactions with neuron-specific proteins (reported as β5-tubulin, creatine kinase B, and protein 14-3-3 ι/β), along with proposed effects on processes linked to neuroplasticity (e.g., signal transduction, energy metabolism, proteolytic protein modification, cell structure, and neuroinflammation).

Key findings (each cites a source)

• A study reported that cortexin inhibited brain caspase-8, while effects on caspase-1, -3, -9, cathepsin B, and calpain were much less pronounced or absent; the study also reported that a peptide fraction isolated from cortexin retained the inhibitory capacity of the original drug and that both cortexin and its fraction prevented neuronal damage in a glutamate-induced cell death culture model. [PMID 28251948]
• A review/article reported that, in an accelerated aging model in rats, cortexin restored the ratio of pro- and antioxidative systems and demonstrated a significant anti-inflammatory effect both in the brain and at the systemic level; it also reported in vitro that cortexin tissue-specifically inhibited brain caspase-8 and that neuron-specific proteins (β5-tubulin, creatine kinase B, and protein 14-3-3 ι/β) were molecular partners of cortexin peptides in the brain. [PMID 30499504]
• A review article described cortexin as containing neuropeptides, amino acids and trace elements, and proposed that its components interact with cellular and molecular “targets” at multiple stages of pathological processes, including processes from synaptic level to epigenetic patterns in the neuron nucleus. [PMID 26356623]
• An in vitro study reported that co-treatment with Cortexin® attenuated high-glucose–induced effects in primary cultured rat sensory neurons in a concentration-dependent manner, using Real-Time Cell Analyzer measurements of cell viability/attachment/neurite outgrowth. [PMID 37080184]
• A study (rabbits with traumatic facial nerve paralysis) reported significant differences between cortexin and methylprednisolone groups versus a saline control group in histopathological measures including neural fibrotic degeneration, myelin degeneration, axonal degeneration, normal myelin production, and edema; it also reported that when comparing cortexin versus methylprednisolone, there was no significant difference except for an increase in collagen fibers, and that electromyography findings did not show significant differences between groups or within groups. [PMID 27819650]
• An open prospective observational study reported improvements over time on neuropsychological testing (MoCA) and reported improvements mainly in attention, short-term memory, and aspects of executive functions in young patients after ischemic stroke receiving a course of Cortexin treatment, with MoCA significance reported at a later visit and SF-36 quality-of-life improvements reported at a subsequent visit and maintained on follow-up visits. [PMID 39269301]
• A review of works devoted to cortexin reported that cortexin was created in 1986 and that favorable effects on cerebral mnestic and cognitive functions in different patient groups were noted, and discussed possible mechanisms involved in recovery of higher nervous activity functions. [PMID 15537099]
• A Cochrane review update (focused on cerebrolysin and cerebrolysin-like agents for acute ischaemic stroke) reported that one included study of a cerebrolysin-like agent (Cortexin) contributed participants, and summarized overall evidence comparisons for cerebrolysin/cerebrolysin-like peptide mixtures on outcomes such as all-cause death, serious adverse events, adverse events, and other outcomes; it also reported specific risk-of-bias judgments for the cortexin study across domains. [PMID 37818733]