Dihexa — Neurotrophic Peptide Research Article (Educational • Research Use Only)

Independent research publication focused on neuroregeneration, peptide innovation, and cognitive biology.

Overview

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a synthetic peptide derivative of Angiotensin IV, designed to study neurotrophic and cognitive-enhancing properties.

Developed by researchers at Washington State University, Dihexa was engineered to overcome limitations in stability and blood–brain-barrier permeability associated with native neuropeptides.

In research contexts, Dihexa has been shown to enhance synaptogenesis, neuronal connectivity, and cognitive performance in animal models, positioning it as a key compound of interest in neurodegenerative and regenerative neuroscience.

Mechanism of Action (Research Context)

Dihexa functions primarily through potentiation of the hepatocyte growth factor (HGF) and c-Met receptor signaling pathway.

This pathway is associated with neuronal survival, differentiation, and synaptic plasticity.

By enhancing the binding affinity between HGF and its receptor c-Met, Dihexa promotes downstream activation of key intracellular cascades, including PI3K/Akt and MAPK/ERK.

These cascades are critical regulators of neurogenesis, dendritic arborization, and synaptic repair.

In preclinical models, Dihexa has demonstrated robust synaptogenic activity, leading to the formation of new dendritic spines and restoration of synaptic density in hippocampal neurons.

This distinguishes Dihexa from traditional cognitive enhancers that modulate neurotransmitter signaling without structural neural regeneration.

Its lipid-soluble structure allows it to cross the blood–brain barrier efficiently, expanding its utility for central nervous system (CNS) research.

Potential Research Benefits (Reported in Literature)

• Promotes synaptogenesis and dendritic spine density in hippocampal neurons

• Enhances cognitive performance and memory retention in preclinical models

• Exhibits neuroprotective effects against oxidative and excitotoxic stress

• Supports neuronal survival and synaptic maintenance in neurodegenerative conditions

• Investigated for applications in Alzheimer’s disease, traumatic brain injury (TBI), and cognitive decline

• Activates HGF/c-Met signaling with low off-target activity in vitro

Selected Research Highlights

• Synaptic Plasticity: In vitro studies show that Dihexa increases synapse formation and improves functional connectivity within hippocampal networks.

• Cognitive Enhancement: Animal models demonstrate significant improvements in maze learning and object-recognition tasks, indicating enhanced long-term potentiation (LTP).

• Neuroprotection: Dihexa-treated neurons exhibit resistance to glutamate-induced excitotoxicity and oxidative damage.

• Regenerative Mechanism: Unlike acetylcholinesterase inhibitors or AMPA modulators, Dihexa repairs neuronal architecture rather than temporarily altering neurotransmission.

Chemical / Physical Information

• Chemical Name: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

• Molecular Formula: C₃₉H₆₆N₆O₆

• Molecular Weight: ~718.98 Da

• Appearance: White crystalline powder

• Solubility: Soluble in DMSO and ethanol; limited solubility in water

• Storage: Lyophilized powder should be stored at −20 °C, protected from light and moisture; reconstituted solutions should be aliquoted and frozen to prevent repeated freeze–thaw cycles.

Regulatory & Compliance Notes

Dihexa is not approved for therapeutic or clinical use by major regulatory agencies.

It is intended solely for research and laboratory applications.

Proper handling requires adherence to institutional biosafety protocols and compliance with relevant chemical-storage and documentation standards, including Certificates of Analysis (COA) and Material Safety Data Sheets (MSDS).

References (Selection)

1. Benoist CC et al. (2014). The neurotrophic compound Dihexa enhances synaptogenesis and improves cognitive function. J Pharmacol Exp Ther.

2. Wright JW, Harding JW. (2015). The brain angiotensin system and Dihexa in neuroregeneration. Front Neurosci.

3. McCoy AT et al. (2013). HGF/c-Met-mediated synaptic plasticity and neuroprotection. Neuroscience.

4. Wright JW et al. (2016). Angiotensin IV analogs as cognitive enhancers and neuroregenerative agents. Curr Med Chem.

5. Chen Q et al. (2017). Peptide-based strategies targeting neurotrophic signaling for CNS repair. Brain Res Bull.

Disclaimer

This article is intended for educational and research purposes only.

Dihexa is not approved for human or veterinary use.

All experiments and studies must comply with institutional, ethical, and legal standards for peptide research and biosafety.

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Selected References

PMID: 23995713 — Dihexa-induced synaptogenesis and cognitive enhancement

PMID: 18603278 — HGF/c-Met pathway activation in neural repair

PMID: 23727840 — Neurotrophic peptide mechanisms and synaptic plasticity

PMID: 29224772 — Peptide-based strategies for CNS regeneration

Frontiers in Neuroscience — Peptide modulation of memory and cognition

Journal of Peptide Science — Neuroactive peptides and brain repair mechanisms

Frequently Asked Questions (FAQ)

Q1: What is Dihexa?A1: Dihexa is a small molecule derivative of angiotensin IV studied for its potential effects on synaptic formation, cognitive pathways, and neural repair in research environments.

Q2: How does Dihexa work in research models?A2: Dihexa is believed to enhance synaptic connectivity by modulating hepatocyte growth factor (HGF) and c-Met signaling, pathways associated with neuronal plasticity.

Q3: Is Dihexa approved for human use?A3: No. Dihexa is an experimental research compound and is not approved for medical, therapeutic, or consumer use.

Q4: What are researchers studying Dihexa for?A4: Research explores Dihexa for cognitive support, neuroplasticity, neural repair, memory enhancement, and models of neurodegenerative processes.

Q5: Does Dihexa cross the blood–brain barrier?A5: Preclinical findings indicate Dihexa may cross the blood–brain barrier efficiently, which is one reason it is highlighted in neural repair research.

Q6: Are there known side effects of Dihexa in studies?A6: Available research is limited, but some studies report no significant acute toxicity; however, long-term safety has not been established.

Q7: How is Dihexa typically evaluated in research?A7: Dihexa is studied in vitro and in animal models that monitor synaptic density, cognitive performance markers, and molecular signaling pathways.

Related Research Compounds

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• BPC-157

• TB-500

• Tesamorelin