Dihexa HGF/c-Met Mechanism - PubMed
Benoist et al./PubMed/2014
Why It Matters
This paper caught my attention because it identifies a specific mechanism for a drug that actually enhances cognition in animals — and it works orally. Most nootropic research either shows weak effects or requires injection. That said, this is preclinical only. No human data exists, and the HGF/c-Met pathway plays complex roles in cancer biology, so safety is a major unknown. Not something you can or should experiment with today, but worth tracking if clinical trials ever materialize.
Key Findings
- Dihexa binds to hepatocyte growth factor (HGF) with high affinity and amplifies its signaling through the c-Met receptor, even at subthreshold HGF concentrations
- Both dihexa and its parent compound Nle(1)-AngIV increased dendritic spine density and synapse formation in rat hippocampal neurons — effects blocked by HGF antagonists
- Orally administered dihexa improved spatial learning in rats on the Morris water maze task by 62% compared to controls, and this effect was eliminated when an HGF antagonist was injected into the brain
- The compound crosses the blood-brain barrier effectively, solving a major pharmacokinetic problem that prevented earlier angiotensin IV analogs from being developed as drugs
- The procognitive effects require functional HGF/c-Met signaling — blocking this pathway with either antagonists or RNA interference eliminated dihexa's benefits
Read the Paper↗PMID: 25187433