Activity-dependent neuroprotective protein–End-binding protein complex (ADNP–EB1/EB3 complex)

The Activity-dependent neuroprotective protein (ADNP)–End-binding protein (EB) complex is a vital protein-protein interaction assembly that regulates microtubule dynamics and stability in neurons. ADNP, a protein essential for brain development, contains a SIP (Ser-Ile-Pro) motif—a variant of the SxIP motif—which mediates its binding to the C-terminal domains of EB1 and EB3 proteins at the plus-ends of microtubules (Oz et al., 2014; Ivashko-Pachima et al., 2017). This interaction is fundamental for axonal transport, dendritic spine density, and overall synaptic plasticity. Disruptions in this complex are linked to neurodegenerative conditions like Alzheimer's disease and neurodevelopmental disorders such as ADNP syndrome (Helsmoortel-Van der Aa syndrome), which is characterized by autism and intellectual disability (Helsmoortel et al., 2014; Gozes, 2011). The therapeutic peptide Davunetide (NAP) is derived from ADNP and contains the SIP motif, allowing it to mimic and stabilize the ADNP-EB interaction. By promoting microtubule-dependent transport and protecting against microtubule disassembly, this complex serves as a key target for neuroprotective interventions (Gozes et al., 2014).

Other names

ADNP-EB1 complexADNP-EB3 complexADNP-EB interactionADNP SxIP motifNAP-EB interaction

Stabilization of the ADNP-EB interaction to enhance microtubule dynamics and protect against tau-related pathology.