Function
While Humanin exerts neuroprotective and cytoprotective effects in models of Alzheimer’s disease, ischemia, and metabolic stress, reducing apoptosis and improving cell survival7136141, 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.
Mechanism
While Humanin works as a mitochondrial-derived 24-amino-acid peptide that protects cells against diverse apoptotic insults by interacting with cell-surface cytokine receptor complexes and intracellular targets, thereby activating pro-survival STAT3 and other pathways7136141, 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.
Length and Sequence
Humanin is 24 amino acids long, whereas Semax is shorter as it has a length of 7 amino acids. Humanin is made up of a sequence of Methionine, Alanine, Proline, Arginine, Glycine, Phenylalanine, Serine, Cysteine, Leucine, Leucine, Leucine, Leucine, Leucine, Threonine, Serine, Glutamic acid, Isoleucine, Aspartic acid, Leucine, Proline, Valine, Lysine, Arginine, Arginine, Alanine. Semax is made up of a sequence of Methionine, Glutamic acid, Histidine, Phenylalanine, Proline, Glycine, Proline.