🧠Dihexa
HGF/MET signalling enhancer. Reported to be 7 orders of magnitude more potent than BDNF at inducing synaptogenesis. Blood-brain barrier penetrant. Used in dementia and cognitive decline research.
N-hexanoic acid-Tyr-Ile-His-Pro-Phe-OHWhat Is Dihexa?
Dihexa is a nonapeptide derivative of angiotensin IV developed at Washington State University. It is a potent HGF/MET system facilitator — binding hepatocyte growth factor (HGF) and potentiating its signalling through the MET receptor tyrosine kinase. It is reportedly 7 orders of magnitude more potent than BDNF at facilitating synaptogenesis, and is highly lipophilic with excellent CNS penetration.
Key Mechanisms
- HGF/MET potentiation — binds HGF and enhances MET receptor signalling in hippocampal neurons
- Synaptogenesis — dramatically increases the formation of new synaptic connections
- Dendritic spine density — increases spine number and morphology in aged and diseased neural models
- Memory formation — facilitates long-term potentiation (LTP) mechanisms
Key References
- McCoy AT et al. "Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents." J Pharmacol Exp Ther, 2013;344(1):141–154.
Frequently Asked Questions
Dihexa isn't BDNF — it's a small peptide derivative of angiotensin IV that potentiates the HGF/MET signalling system, which converges on some of the same synaptogenesis pathways BDNF uses, but through a separate receptor mechanism and with much greater blood-brain-barrier penetration than BDNF protein itself.
Unlike many neurotrophic peptides, Dihexa's high lipophilicity lets it cross the blood-brain barrier after peripheral administration in animal models, which is one of the main reasons it has attracted research interest as a systemically deliverable cognitive compound.
Preclinical work has focused primarily on rodent models of aging-related cognitive decline and dementia, evaluating synaptogenesis and spatial memory performance.