ArticlePloS one2019
NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- ADNP Functions During Early Brain Development and Their Relevance to ASD and ADNP Syndrome.International journal of molecular sciences · 2026Review
- Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.ACS omega · 2025Review
- Extremely Low-Frequency and Low-Intensity Electromagnetic Field Technology (ELF-EMF) Sculpts Microtubules.The European journal of neuroscience · 2025Article
- Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.Translational psychiatry · 2023Article
- Article
- The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling.Molecular psychiatry · 2023Article
- Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye.International journal of molecular sciences · 2022Review
- SH3- and actin-binding domains connect ADNP and SHANK3, revealing a fundamental shared mechanism underlying autism.Molecular psychiatry · 2022Article
- Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living.Journal of molecular neuroscience : MN · 2022Article
- Parkinson Disease-Modification Encompassing Rotenone and 6-Hydroxydopamine Neurotoxicity by the Microtubule-Protecting Drug Candidate SKIP.Journal of molecular neuroscience : MN · 2021Article
- Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study.Molecular psychiatry · 2021Article
- Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration.Journal of experimental pharmacology · 2021Review
- Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories.Frontiers in molecular neuroscience · 2021Article
- Sex-and Region-Dependent Expression of the Autism-Linked ADNP Correlates with Social- and Speech-Related Genes in the Canary Brain.Journal of molecular neuroscience : MN · 2020Article
- Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting.Cells · 2020Article
- Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP.International journal of molecular sciences · 2020Article
- Deciphering the Enigma: NAP (CP201) the Active ADNP Drug Candidate Enters Cells by Dynamin-Associated Endocytosis.Journal of molecular neuroscience : MN · 2020Article
- The ADNP Syndrome and CP201 (NAP) Potential and Hope.Frontiers in neurology · 2020Review
- Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings.Journal of Alzheimer's disease reports · 2019Review
- Intraneuronal Tau Misfolding Induced by Extracellular Amyloid-β Oligomers.Journal of Alzheimer's disease : JAD · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The microtubule (MT) associated protein Tau is instrumental for the regulation of MT assembly and dynamic instability, orchestrating MT-dependent cellular processes. Aberration in Tau post-translational modifications ratio deviation of spliced Tau isoforms 3 or 4 MT binding repeats (3R/4R) have been implicated in neurodegenerative tauopathies. Activity-dependent neuroprotective protein (ADNP) is vital for brain formation and cognitive function. ADNP deficiency in mice causes pathological Tau hyperphosphorylation and aggregation, correlated with impaired cognitive functions. It has been previously shown that the ADNP-derived peptide NAP protects against ADNP deficiency, exhibiting neuroprotection, MT interaction and memory protection. NAP prevents MT degradation by recruitment of Tau and end-binding proteins to MTs and expression of these proteins is required for NAP activity. Clinically, NAP (davunetide, CP201) exhibited efficacy in prodromal Alzheimer's disease patients (Tau3R/4R tauopathy) but not in progressive supranuclear palsy (increased Tau4R tauopathy). Here, we examined the potential preferential interaction of NAP with 3R vs. 4R Tau, toward personalized treatment of tauopathies. Affinity-chromatography showed that NAP preferentially interacted with Tau3R protein from rat brain extracts and fluorescence recovery after photobleaching assay indicated that NAP induced increased recruitment of human Tau3R to MTs under zinc intoxication, in comparison to Tau4R. Furthermore, we showed that NAP interaction with tubulin (MTs) was inhibited by obstruction of Tau-binding sites on MTs, confirming the requirement of Tau-MT interaction for NAP activity. The preferential interaction of NAP with Tau3R may explain clinical efficacy in mixed vs. Tau4R pathologies, and suggest effectiveness in Tau3R neurodevelopmental disorders.
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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.