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Study · Animal study (in vivo) · mouse · 2014

7 results

Intranasal NAP (davunetide) decreases tau hyperphosphorylation and moderately improves behavioral deficits in mice overexpressing α-synuclein.

Magen I, Ostritsky R, Richter F, Zhu C, Fleming SM, Lemesre V, Stewart AJ, Morimoto BH, Gozes I, Chesselet MF

Pharmacology research & perspectives6 Aug 2014Cited by 38 (Europe PMC)

PMID25505609 (opens in a new tab)PMCIDPMC4186425 (opens in a new tab)DOI10.1002/prp2.65 (opens in a new tab)PepBankPUB-25505609
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Summary

Genome-wide association studies have identified strong associations between the risk of developing Parkinson's disease (PD) and polymorphisms in the genes encoding α-synuclein and the microtubule-associated protein tau. However, the contribution of tau and its phosphorylated form (p-tau) to α-synuclein-induced pathology and neuronal dysfunction remains controversial. We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD. We found that the p-tau/tau level increased in a subcortical tissue block that includes the striatum and brain stem, and in the cerebellum of the Thy1-aSyn mice compared to nontransgenic controls. Intermittent intranasal NAP administration at 2 μg/mouse per day, 5 days a week, for 24 weeks, starting at 4 weeks of age, significantly decreased the ratio of p-tau/tau levels in the subcortical region while a higher dose of 15 μg/mouse per day induced a decrease in p-tau/tau levels in the cerebellum. Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug. The data reveal novel effects of NAP on brain p-tau/tau and behavioral outcomes in this model of synucleinopathy and suggest that sustained exposure to NAP may be necessary for maximal benefits.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In Thy1-aSyn mice, NAP at 2 μg/mouse per day significantly decreased the subcortical p-tau/tau ratio.

    In plain wordsIn mice overexpressing α-synuclein, the lower NAP dose decreased the subcortical p-tau/tau ratio.

    Peptide
    Davunetide
    Outcome
    DecreaseSubcortical p-tau/tau ratio
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    2 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Intermittent intranasal NAP administration at 2 μg/mouse per day, 5 days a week, for 24 weeks, starting at 4 weeks of age, significantly decreased the ratio of p-tau/tau levels in the subcortical region while a higher dose of 15 μg/mouse per day induced a decrease in p-tau/tau levels in the cerebellum.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In Thy1-aSyn mice, NAP at 15 μg/mouse per day decreased cerebellar p-tau/tau levels.

    In plain wordsIn mice overexpressing α-synuclein, the higher NAP dose decreased cerebellar p-tau/tau levels.

    Peptide
    Davunetide
    Outcome
    DecreaseCerebellar p-tau/tau levels
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Intermittent intranasal NAP administration at 2 μg/mouse per day, 5 days a week, for 24 weeks, starting at 4 weeks of age, significantly decreased the ratio of p-tau/tau levels in the subcortical region while a higher dose of 15 μg/mouse per day induced a decrease in p-tau/tau levels in the cerebellum.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In Thy1-aSyn mice, both NAP doses reduced hyperactivity.

    In plain wordsIn mice overexpressing α-synuclein, both NAP doses reduced hyperactivity.

    Peptide
    Davunetide
    Outcome
    DecreaseHyperactivity
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    2 and 15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In Thy1-aSyn mice, both NAP doses improved habituation to a novel environment.

    In plain wordsIn mice overexpressing α-synuclein, both NAP doses improved habituation to a new environment.

    Peptide
    Davunetide
    Outcome
    IncreaseHabituation to a novel environment
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    2 and 15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In Thy1-aSyn mice, both NAP doses reduced olfactory deficits.

    In plain wordsIn mice overexpressing α-synuclein, both NAP doses reduced smell deficits.

    Peptide
    Davunetide
    Outcome
    DecreaseOlfactory deficits
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    2 and 15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In Thy1-aSyn mice, neither NAP dose improved motor coordination deficits on the challenging beam.

    In plain wordsIn mice overexpressing α-synuclein, neither NAP dose improved coordination on the challenging beam.

    Peptide
    Davunetide
    Outcome
    No significant changeChallenging beam motor coordination deficits
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    2 and 15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In Thy1-aSyn mice, neither NAP dose improved motor coordination deficits on the pole.

    In plain wordsIn mice overexpressing α-synuclein, neither NAP dose improved coordination on the pole.

    Peptide
    Davunetide
    Outcome
    No significant changePole motor coordination deficits
    Study

    mousen: not reported in source

    Thy1-aSyn mice
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    2 and 15 μg/mouse per day, 5 days a week · intranasal · 24 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug.
    1 context sentence
    Summary · context
    We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

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