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Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs)

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ADNP Functions During Early Brain Development and Their Relevance to ASD and ADNP Syndrome.

Xiaonan Liu¹, Shiena Watanabe¹, Sierra Coleman¹

¹Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.

International Journal of Molecular Sciences

|July 15, 2026

Summary

Activity-Dependent Neuroprotective Protein (ADNP) regulates brain development and neurite formation. Its peptide NAP shows therapeutic potential for neurodevelopmental disorders like autism spectrum disorder (ASD) and ADNP syndrome.

Keywords:

ADNP ADNP syndrome NAP autism spectrum disorder cortical development early brain development microtubule dynamics neurite formation neurogenesis

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Area of Science:

Neuroscience
Developmental Biology
Genetics

Background:

Activity-Dependent Neuroprotective Protein (ADNP) is crucial for early brain development, including cortical neurogenesis and neurite formation.
Mutations in the ADNP gene cause ADNP syndrome (Helsmoortel-Van der Aa syndrome), a leading single-gene cause of syndromic autism spectrum disorder (ASD) and intellectual disability.
ADNP functions as both a transcription factor regulating gene expression and a microtubule (MT) regulator controlling neurite outgrowth.

Purpose of the Study:

To review the functions of full-length ADNP and its derived peptide NAP in early brain development, focusing on neurogenesis and neurite formation.
To discuss the therapeutic potential of NAP for neurodevelopmental disorders, particularly ASD and ADNP syndrome.

Main Methods:

Review of existing literature on ADNP, ADNP syndrome, and NAP (Davunetide).
Analysis of ADNP's roles in chromatin remodeling (ChAHP, SWI/SNF) and Wnt/β-catenin signaling.
Examination of ADNP's cytoplasmic function as an MT regulator through interactions with EB1, EB3, and Tau.

Main Results:

ADNP plays a dual role: nuclear transcription factor and cytoplasmic MT regulator.
ADNP's nuclear functions involve chromatin remodeling and modulating signaling pathways essential for development.
ADNP's cytoplasmic functions, involving binding to EB proteins and Tau, are critical for neurite formation during neural differentiation.

Conclusions:

Full-length ADNP and its peptide NAP are vital for neurogenesis and neurite formation during cortical development.
NAP demonstrates significant therapeutic promise for treating neurodevelopmental disorders, including ASD and ADNP syndrome.
Further research into ADNP and NAP could lead to novel therapeutic strategies for brain development disorders.