NAP (Davunetide) Extended Notes

Also known as: AL-108, ADNP peptide, NAPVSIPQ

NeuroprotectiveCognitive & Nootropic

Overview

NAP (NAPVSIPQ) represents a critical bridge between VIP-based neuroprotection and practical clinical peptide therapeutics. The discovery that a single 8-amino acid sequence from the ADNP protein (activity-dependent neuroprotective protein) could recapitulate much of VIP's neuroprotective activity led to development of davunetide as an intranasal therapeutic. ADNP haploinsufficiency causes the ADNP syndrome (Helsmoortel-Van der Aa syndrome), a rare autism spectrum disorder characterized by intellectual disability and is caused by de novo mutations, confirming ADNP/NAP as essential for brain development. These genetic findings have revitalized clinical interest.

Mechanism of Action

NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) interacts directly with tubulin heterodimers, stabilizing microtubule polymerization and preventing tau-mediated microtubule destabilization. It also interacts with SIP (SH2-domain containing inositol phosphatase) to regulate PI3K/Akt survival signaling. In ADNP syndrome models, NAP restores normal dendritic spine morphology, reduces hyperphosphorylated tau, and normalizes autophagy. The intranasal route provides efficient CNS delivery via olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier.

Potential Benefits

  • Microtubule stabilization preventing tau pathology
  • Potential treatment for ADNP syndrome (rare autism disorder)
  • Neuroprotection in Alzheimer's disease models
  • PSP (progressive supranuclear palsy) clinical trials conducted
  • Intranasal delivery is non-invasive and efficient

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Intranasal: 3 mg twice daily (PSP trials). ADNP syndrome trials dosing under investigation.

Amino Acid Sequence

Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln

Side Effects & Safety

  • Intranasal: mild nasal irritation
  • Well-tolerated in clinical trials

Synergistic Compounds

The following compounds have been studied alongside NAP (Davunetide) Extended Notes for potential complementary or synergistic effects:

VIPCerebrolysinSemax

Learn More

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References & Further Reading

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SelankSemaxDSIPHumaninDihexaCerebrolysin