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Study · In vitro (cells) · 2023

4 results

NAP (Davunetide): The Neuroprotective ADNP Drug Candidate Penetrates Cell Nuclei Explaining Pleiotropic Mechanisms.

Ganaiem M, Gildor ND, Shazman S, Karmon G, Ivashko-Pachima Y, Gozes I

Cells11 Sept 2023Cited by 16 (Europe PMC)

PMID37759476 (opens in a new tab)PMCIDPMC10527813 (opens in a new tab)DOI10.3390/cells12182251 (opens in a new tab)PepBankPUB-37759476
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Summary

(1) Background: Recently, we showed aberrant nuclear/cytoplasmic boundaries/activity-dependent neuroprotective protein (ADNP) distribution in ADNP-mutated cells. This malformation was corrected upon neuronal differentiation by the ADNP-derived fragment drug candidate NAP (davunetide). Here, we investigated the mechanism of NAP nuclear protection. (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*). Cells were exposed to NAP conjugated to Cy5, followed by live imaging. Cells were further characterized using quantitative morphology/immunocytochemistry/RNA and protein quantifications. (3) Results: NAP rapidly distributed in the cytoplasm and was also seen in the nucleus. Furthermore, reduced microtubule content was observed in the ADNP-mutated cell lines. In parallel, disrupting microtubules by zinc or nocodazole intoxication mimicked ADNP mutation phenotypes and resulted in aberrant nuclear-cytoplasmic boundaries, which were rapidly corrected by NAP treatment. No NAP effects were noted on ADNP levels. Ketamine, used as a control, was ineffective, but both NAP and ketamine exhibited direct interactions with ADNP, as observed via in silico docking. (4) Conclusions: Through a microtubule-linked mechanism, NAP rapidly localized to the cytoplasmic and nuclear compartments, ameliorating mutated ADNP-related deficiencies. These novel findings explain previously published gene expression results and broaden NAP (davunetide) utilization in research and clinical development.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

  1. 01LabIn vitro (cells)Pharmacokinetics

    In N1E-115 cells, Cy5-conjugated NAP rapidly distributed in the cytoplasm.

    In plain wordsIn cells, Cy5-conjugated NAP rapidly distributed in the cytoplasm.

    Peptide
    Davunetide
    Outcome
    Not applicableCytoplasmic distribution
    Study

    n: not reported in source

    N1E-115 neuroblastoma cells expressing mutated ADNP
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    (3) Results: NAP rapidly distributed in the cytoplasm and was also seen in the nucleus.
    2 context sentences
    Summary · context
    (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*).
    Summary · context
    Cells were exposed to NAP conjugated to Cy5, followed by live imaging.
  2. 02LabIn vitro (cells)Pharmacokinetics

    In N1E-115 cells, Cy5-conjugated NAP was detected in the nucleus.

    In plain wordsIn cells, Cy5-conjugated NAP was detected in the nucleus.

    Peptide
    Davunetide
    Outcome
    Not applicableNuclear distribution
    Study

    n: not reported in source

    N1E-115 neuroblastoma cells expressing mutated ADNP
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    (3) Results: NAP rapidly distributed in the cytoplasm and was also seen in the nucleus.
    2 context sentences
    Summary · context
    (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*).
    Summary · context
    Cells were exposed to NAP conjugated to Cy5, followed by live imaging.
  3. 03LabIn vitro (cells)Mechanism

    In cells with zinc- or nocodazole-disrupted microtubules, NAP rapidly corrected aberrant nuclear-cytoplasmic boundaries.

    In plain wordsIn cells with disrupted microtubules, NAP rapidly corrected abnormal boundaries between the nucleus and cytoplasm.

    Peptide
    Davunetide
    Outcome
    Direction not reportedNuclear-cytoplasmic boundary abnormalities
    Study

    n: not reported in source

    Cells with zinc- or nocodazole-disrupted microtubules
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In parallel, disrupting microtubules by zinc or nocodazole intoxication mimicked ADNP mutation phenotypes and resulted in aberrant nuclear-cytoplasmic boundaries, which were rapidly corrected by NAP treatment.
    2 context sentences
    Summary · context
    (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*).
    Summary · context
    Cells were exposed to NAP conjugated to Cy5, followed by live imaging.
  4. 04LabIn vitro (cells)Mechanism

    In N1E-115 cell experiments, NAP had no observed effects on ADNP levels.

    In plain wordsIn cells, NAP had no observed effect on ADNP levels.

    Peptide
    Davunetide
    Outcome
    No significant changeADNP levels
    Study

    n: not reported in source

    N1E-115 neuroblastoma cells expressing mutated ADNP
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No NAP effects were noted on ADNP levels.
    2 context sentences
    Summary · context
    (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*).
    Summary · context
    Cells were exposed to NAP conjugated to Cy5, followed by live imaging.

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

Subjects

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