Davunetide
clinical trialsAlso known as: NAP, AL-108
Davunetide (NAP, AL-108) is an eight-amino-acid peptide fragment derived from the activity-dependent neuroprotective protein (ADNP). Its primary mechanism of action involves binding to and stabilizing microtubules, thereby promoting cytoskeletal integrity and neuronal survival. This microtubule-stabilizing effect is thought to counteract tau pathology and axonal transport deficits, which are central to neurodegenerative diseases. Additionally, davunetide has been shown to modulate synaptic plasticity and reduce oxidative stress in preclinical models. Key research findings from 78 PubMed-indexed studies indicate that davunetide improves cognitive function and reduces tau hyperphosphorylation in animal models of tauopathy. In clinical trials, it demonstrated safety and tolerability, with some evidence of cognitive benefit in patients with progressive supranuclear palsy (PSP) and schizophrenia. However, a Phase II/III trial in PSP did not meet its primary endpoint, though secondary analyses suggested potential efficacy in subgroups. Ongoing research continues to explore its utility in tauopathies and neuropsychiatric disorders. Clinically, davunetide has been investigated for conditions involving microtubule dysfunction, including PSP, Alzheimer’s disease, and schizophrenia. While not yet approved for any indication, it represents a promising candidate for neuroprotection and cognitive enhancement. Further trials are needed to confirm efficacy and identify optimal patient populations. For research purposes only — not medical advice.
Key data
C36H60N10O12Research & studies
NAP enhances microtubule stability and prevents tauopathy in preclinical models.; Intranasal delivery of NAP is safe, bioavailable, and shows potential cognitive benefits in clinical studies.; In a phase II-III trial for progressive supranuclear palsy, NAP significantly slowed disease progression in women.; ADNP deficiency is compensated by NAP, highlighting its role in regulating circadian rhythms and tauopathy pathways.
Men had significant dose-dependent cognitive increases in delayed visual matching to sample.; Women showed a low-dose placebo effect and high-dose davunetide improvement in digit span working memory.; Anxiety correlated with cognition in opposite ways between sexes, with women showing significant correlations in delayed matching.
ADNP was significantly downregulated in neonatal mice after sevoflurane exposure.; Sevoflurane reduced dendrite number, spine density, and synaptic protein expression in the ACC.; Davunetide treatment reversed synaptic defects, social behavior deficits, and cognitive impairments.; Mechanistically, ADNP loss disrupted Ca2+ activity via Wnt/β-catenin signaling, which was restored by davunetide.
VIP regulates ADNP, linking to the original discovery of ADNP and its active neuroprotective site NAP (davunetide).; Tau-ADNP-NAP interactions are central, with sex influencing these relationships.; The perspective highlights future directions in translational medicine based on these interactions.
Females on placebo showed dramatic baseline ventricular volume-dependent increases at 52 weeks (r=0.74, P=2.36e-9), while davunetide-treated females showed no such effects.; Davunetide slowed female disease progression, with significant protection on the SEADL scale by 39 weeks (P=0.008) and on bulbar/limb motor domains by 52 weeks (P=0.01).; The Geriatric Depression Scale correlated with SEADL deterioration in female placebo group, and davunetide provided protection in females.; Men showed significantly slower disease progression overall, highlighting sex-based efficacy differences.
Davunetide reversed Aβ1-42-induced spatial learning and memory deficits in a dose-dependent manner in the Morris water maze.; Davunetide blocked Aβ1-42-induced suppression of long-term potentiation in the hippocampal CA1 region without affecting paired-pulse facilitation.; Davunetide antagonized the decrease in hippocampal p-AKT (Ser473) levels caused by Aβ1-42.; Findings suggest davunetide may be a therapeutic candidate for Alzheimer's disease by enhancing PI3K/AKT signaling.
Frequently asked questions
What is Davunetide?
Davunetide (NAP, AL-108) is an eight-amino-acid peptide fragment derived from the activity-dependent neuroprotective protein (ADNP). Its primary mechanism of action involves binding to and stabilizing microtubules, thereby promoting cytoskeletal integrity and neuronal survival. This microtubule-stabilizing effect is th
How does Davunetide work?
8-aa fragment of activity-dependent neuroprotective protein (ADNP) that stabilizes microtubules; trialed in PSP and schizophrenia.
What is the research status of Davunetide?
Davunetide is currently classified as clinical trials, with 80 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Davunetide?
Davunetide has a molecular weight of approximately 824.9 g/mol (formula C36H60N10O12).
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