Ingredient or product comparison
Mechanism of Action: BDNF-TrkB vs Nrf2-ARE — Two Orthogonal Neuroprotective Systems
Semax (Met-Glu-His-Phe-Pro-Gly-Pro, MW ~813 Da) is a heptapeptide ACTH₄₋₇ analogue that potently upregulates BDNF synthesis in neurons and astrocytes. The sequence of events: Semax binds melanocortin receptors (primarily MC4R, with partial MC3R activity) on co
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- Semax (Met-Glu-His-Phe-Pro-Gly-Pro, MW ~813 Da) is a heptapeptide ACTH₄₋₇ analogue that potently upregulates BDNF synthesis in neurons and astrocytes. The sequence of events: Semax binds melanocortin receptors (primarily MC4R, with partial MC3R activity) on cortical and hippocampal neurons, activating Gαs-cAMP-PKA-CREB and Gαq-PLC-IP₃-Ca²⁺ signalling. CREB phosphorylation at Ser-133 drives transcription of the BDNF exon IV promoter, increasing BDNF mRNA within 1–2 hours and protein within 6–12 hours. Released BDNF then acts in an autocrine/paracrine manner at TrkB (NTRK2) receptors, activating PI3K-Akt-mTOR (survival/anti-apoptotic) and MAPK-ERK (differentiation/plasticity) downstream cascades. The full signalling cascade requires 6–24 hours for measurable neuroprotective effect — Semax is a transcriptionally driven neuroprotectant with delayed but sustained action.
- GHK-Cu (glycyl-L-histidyl-L-lysine copper II, MW ~340 Da including Cu²⁺) accesses neuroprotection via a fundamentally different entry point: Nrf2 (nuclear factor erythroid 2-related factor 2) activation. The copper-peptide complex is imported into neurons via the copper transporter Ctr1 (SLC31A1) and potentially via direct membrane permeation. Once intracellular, GHK-Cu oxidises Keap1 cysteine residues (C273, C288), releasing Nrf2 from Keap1 ubiquitination and allowing nuclear translocation. Nrf2 binds the antioxidant response element (ARE) in gene promoters within 2–4 hours, driving transcription of HO-1 (heme oxygenase-1), NQO1 (NAD(P)H:quinone oxidoreductase-1), ferritin, glutamate-cysteine ligase (GCL), and thioredoxin reductase. This produces a broad-spectrum enzymatic antioxidant defence that directly counteracts oxidative stress — the primary acute injury signal in ischaemia, trauma and excitotoxicity. GHK-Cu also directly chelates redox-active iron and copper in the extracellul