ArticleMolecular psychiatry2016
Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 89 citations in OpenAlex.
- Systemic davunetide provides sex-specific neuroprotection during Coronary Artery Bypass Grafting (CABG).Translational psychiatry · 2025Trial
- Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease.Translational psychiatry · 2024Trial
- Opposite molecular sex correlations in tauopathy paralleled by motor and cognitive efficacy of davunetide in women.Molecular psychiatry · 2026Article
- Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice.Molecular psychiatry · 2026Article
- ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.Molecular psychiatry · 2025Article
- Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP.Neurogenetics · 2025Article
- Extremely Low-Frequency and Low-Intensity Electromagnetic Field Technology (ELF-EMF) Sculpts Microtubules.The European journal of neuroscience · 2025Article
- Oxidative Stress Promotes Axonal Atrophy through Alterations in Microtubules and EB1 Function.Aging and disease · 2024Article
- Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.Journal of molecular neuroscience : MN · 2024Article
- Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice.Zoological research · 2024Article
- ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel-Van der Aa syndrome autopsy case.Acta neuropathologica communications · 2024Article
- Moderate Physical Activity Increases the Expression of ADNP in Rat Brain.International journal of molecular sciences · 2024Article
- Longitudinal Genotype-Phenotype (Vineland Questionnaire) Characterization of 15 ADNP Syndrome Cases Highlights Mutated Protein Length and Structural Characteristics Correlation with Communicative Abilities Accentuated in Males.Journal of molecular neuroscience : MN · 2024Article
- Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.Translational psychiatry · 2023Article
- Article
- Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits.Molecular psychiatry · 2023Article
- The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling.Molecular psychiatry · 2023Article
- Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism.Clinical epigenetics · 2023Review
- Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye.International journal of molecular sciences · 2022Review
- Distinct Impairments Characterizing Different ADNP Mutants Reveal Aberrant Cytoplasmic-Nuclear Crosstalk.Cells · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences. RNA sequencing evaluations showed major age, sex and genotype differences. Function enrichment and focus on major gene expression changes further implicated channel/transporter function and the cytoskeleton. In particular, a significant maturation change (1 month-five months) was observed in beta1 tubulin (Tubb1) mRNA, only in Adnp(+/+) males, and sex-dependent increase in calcium channel mRNA (Cacna1e) in Adnp(+/+) males compared with females. At the protein level, the Adnp(+/-) mice exhibited impaired hippocampal expression of the calcium channel (voltage-dependent calcium channel, Cacnb1) as well as other key ASD-linked genes including the serotonin transporter (Slc6a4), and the autophagy regulator, BECN1 (Beclin1), in a sex-dependent manner. Intranasal SKIP treatment normalized social memory in 8- to 9-month-old Adnp(+/-)-treated mice to placebo-control levels, while protecting axonal transport and ameliorating changes in ASD-like gene expression. The control, all d-amino analog D-SKIP, did not mimic SKIP activity. SKIP presents a novel prototype for potential ASD drug development, a prevalent unmet medical need.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.