Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-induced Huntington's Disease-Like Symptoms in Rats
Summary
Tested whether PNB-0408 (a Dihexa-related angiotensin IV analog) could protect against 3-nitropropionic acid-induced Huntington's disease-like neurotoxicity in rats. The compound did not demonstrate significant neuroprotective effects in this model, suggesting limitations of the HGF/c-Met approach for mitochondrial toxin-mediated neurodegeneration.
Key Findings
- Angiotensin IV analog did not significantly protect against 3-NP-induced neurotoxicity
- Suggests HGF/c-Met activation may be insufficient for mitochondrial toxin-mediated neurodegeneration
- Provides important negative data on scope of angiotensin IV analogs in neurodegeneration
Access Full Text
Read the complete published study from the original source.
View on Publisher SiteRelated Monographs
Available Research Products
Related Studies
View all →Procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system
Benoist CC, Kawas LH, Zhu M, et al.
Journal of Pharmacology and Experimental Therapeutics
Demonstrated that Dihexa (norleucine-angiotensin IV) binds hepatocyte growth factor (HGF) and induces hippocampal spinogenesis and synaptogenesis through the HGF/c-Met receptor system. Procognitive effects of Dihexa were blocked by the HGF antagonist Hinge, confirming HGF/c-Met as the primary mechanism.
- Dihexa binds HGF and activates the c-Met receptor system to promote synaptogenesis
- Induced hippocampal dendritic spinogenesis and new synapse formation
A novel angiotensin IV/AT4 receptor ligand, Nle1-AngIV (dihexa), is a potent procognitive agent that augments hepatocyte growth factor (HGF)/Met signaling
McCoy AT, Benoist CC, Wright JW, et al.
Journal of Pharmacology and Experimental Therapeutics
This study characterized dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide), a stable angiotensin IV analog, as a potent procognitive compound that operates through the HGF/c-Met receptor system. Dihexa demonstrated cognitive-enhancing effects at picomolar concentrations, approximately seven orders of magnitude more potent than BDNF, in scopolamine-induced memory impairment models.
- Dihexa crossed the blood-brain barrier and improved cognitive performance in scopolamine-induced amnesia models at doses as low as 2 pmol via intracerebroventricular administration
- The procognitive mechanism was identified as augmentation of HGF/c-Met receptor signaling, promoting dendritic spine formation and synaptogenesis