ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease

Activity-dependent neuroprotective protein (ADNP), discovered in our laboratory in 1999, has been characterized as a master gene vital for mammalian brain formation. ADNP de novo mutations in humans result in a syndromic form of autism-like spectrum disorder (ASD), including cognitive and motor deficits, the ADNP syndrome (Helsmoortel-Van Der Aa). One of the most important cellular processes associated with ADNP is the autophagy pathway, recently discovered by us as a key player in the pathophysiology of schizophrenia. In this regard, given the link between the microtubule and autophagy systems, the ADNP microtubule end binding protein motif, namely, the neuroprotective NAP (NAPVSIPQ), was found to enhance autophagy while protecting microtubules and augmenting ADNP's association with both systems. Thus, linking autophagy and ADNP is proposed as a major target for intervention in brain diseases from autism to Alzheimer's disease (AD) and our findings introduce autophagy as a possible novel target for treating schizophrenia.

Activity-dependent neuroprotective protein (ADNP) binds to microtubule-associated protein light chain 3, which forms the membrane of the autophagosome, a key organelle in the autophagy process and regulates beclin1 (BECN1) formation, an inducer of autophagy. Autophagy plays a major role in Alzheimer's disease and as recently discovered in schizophrenia and autism.

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