Activity-dependent neuroprotective protein (ADNP)

Activity-dependent neuroprotective protein (ADNP) is a multifunctional protein essential for brain development, cognitive function, and cellular survival [1, 11]. It operates as both a transcription factor within the SWI/SNF chromatin remodeling complex and a cytoplasmic regulator of the microtubule cytoskeleton, where it interacts with end-binding proteins (EB1 and EB3) to maintain axonal transport and synaptic plasticity [3, 5, 7]. Mutations in the ADNP gene are the primary cause of ADNP syndrome (Helsmoortel-Van der Aa syndrome), a condition characterized by autism spectrum disorder, intellectual disability, and motor delays [2, 4]. Additionally, dysregulation of ADNP expression and somatic mutations have been linked to neurodegenerative diseases like Alzheimer's and Parkinson's, and neuropsychiatric disorders such as schizophrenia [8, 11, 14]. Therapeutic development has centered on ADNP-derived peptides, particularly Davunetide (NAP), which mimics the protein's neuroprotective 'SxIP' motif to stabilize microtubules and prevent tauopathy [5, 7, 11]. Because of its involvement in essential biological pathways like autophagy and gene regulation, ADNP serves as a critical focus for neuroprotective drug discovery and as a potential blood-borne biomarker for tracking neurodegeneration [2, 8, 13].

Other names

Activity-dependent neuroprotector homeobox proteinADNPHelsmoortel-Van der Aa syndrome protein

Drugs targeting or derived from ADNP, such as Davunetide (NAP), primarily function by stabilizing microtubules through interaction with end-binding proteins (EB1 and EB3) and enhancing Tau-microtubule binding [3, 7, 11]. These agents also promote autophagy by facilitating the interaction between ADNP and LC3 and modulate the transcription of hundreds of protective genes via the SWI/SNF chromatin remodeling complex [2, 5, 13].