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

gene result in ADNP syndrome, which is also known as Helsmoortel-Van der Aa syndrome, a complex neurodevelopmental disorder recognized as a leading single-gene cause of syndromic autism spectrum disorder (ASD) and intellectual disability. ADNP works as both a transcription factor and a microtubule (MT) regulator. As a transcription factor, ADNP is a key component of chromatin remodeling complexes such as ChAHP (CHD4 (Chromodomain Helicase DNA-binding Protein 4)-ADNP-HP1 (Heterochromatin Protein 1)) and SWI/SNF (Switch/Sucrose Non-Fermentable), and it tightly regulates the expression of numerous essential developmental genes. ADNP also modulates the Wnt/β-catenin signaling pathway. During neural differentiation, ADNP is redistributed from the nucleus to the cytoplasm, and this redistribution is regulated by binding to 14-3-3 proteins, which are phosphorylated by protein Kinase C (PKC). After relocating to the cytoplasm, ADNP functions as an MT regulator by binding to microtubule end-binding proteins (EB1 and EB3) and Tau to control neurite formation. Previous studies have focused on NAP (also known as Davunetide, a peptide derived from ADNP) in MT regulation and its therapeutic potential for autism spectrum disorder (ASD) and neurodegenerative diseases, such as Alzheimer's disease. This review highlights the functions of full-length ADNP and NAP in early brain development, particularly in neurogenesis and neurite formation during cortical development. We will also discuss the potential of NAP as a therapeutic medication for neurodevelopmental disorders, especially ASD and ADNP syndrome.