Comparison
While MOTS-c improves insulin sensitivity, enhances glycolysis, reduces oxidative stress, and shows protective effects in models of metabolic syndrome, aging, and ischemia-reperfusion injury8135146, Semax is used clinically in Russia for ischemic stroke and cognitive disorders; in models it improves learning, protects dopaminergic neurons, and modulates stress responses without significant endocrine ACTH-like effects166174.
While MOTS-c works as a 16-amino-acid mitochondrial-derived peptide that translocates to the nucleus under metabolic stress and regulates glucose and lipid metabolism largely via activation of AMPK and modulation of mTOR and folate-cycle–linked pathways854140146, Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), that is an analog of ACTH(4–10) with a Pro-Gly-Pro extension and exerts neurotrophic and neuroprotective actions partly via upregulation of BDNF and modulation of dopaminergic and glutamatergic systems40162165174.
MOTS-c is 16 amino acids long, whereas Semax is shorter as it has a length of 7 amino acids. MOTS-c is made up of a sequence of Methionine, Arginine, Tryptophan, Glutamine, Glutamic acid, Methionine, Glycine, Tyrosine, Isoleucine, Phenylalanine, Tyrosine, Proline, Arginine, Lysine, Leucine, Arginine. Semax is made up of a sequence of Methionine, Glutamic acid, Histidine, Phenylalanine, Proline, Glycine, Proline.
MOTS-c
Semax
Targets are not fully defined; interacts with melanocortin-related pathways and inhibits certain peptidases, but no single dominant receptor has been established174
MOTS-c
MT-RNR1
Semax
POMC
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