PE-22-28 is a synthetic analog of spadin that blocks TREK-1 potassium channels — a novel antidepressant mechanism completely distinct from SSRIs, SNRIs, or any approved psychiatric drug. The animal data is promising. The human data does not exist.
Dihexa is reported to be seven orders of magnitude more potent than BDNF itself at promoting synaptogenesis in cell culture. It also has essentially no human data. That tension — extraordinary in vitro potency, near-zero clinical evidence — defines everything you need to know about where to place it.
SS-31 concentrates in the inner mitochondrial membrane at 1,000-fold plasma levels and protects cardiolipin — the phospholipid that holds the electron transport chain together. It has reached Phase II human trials for heart failure. Supply is limited and quality control is a serious concern.
Humanin is a mitochondrially-encoded peptide whose circulating levels in humans predict cardiovascular risk, Alzheimer's risk, and longevity. It declines with age in every tissue and population studied. The intervention evidence is still animal-only — but the observational case is among the strongest in longevity biology.
MOTS-c is encoded in the mitochondrial genome — not the nuclear genome — making it one of the most unusual peptides in biology. It declines with age, correlates with longevity markers in human populations, and mimics exercise at the molecular level.
Cerebrolysin is the only compound in this review series with multiple Cochrane reviews and regulatory approval in Europe and Asia. It is a peptide mixture, not a defined molecule — which makes it harder to characterise and harder to source reliably.