The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse

• DOI: 10.1038/s41398-018-0357-6
• Publication Date: 2019-01-21T11:02:40Z
• Authors: Shlomo Sragovich; Anna Malishkevich; Yael Piontkewitz; Eliezer Giladi; Olga Touloumi; Roza Lagoudaki; Nikolaos Grigoriadis; Illana Gozes
• Keywords: Nap

Abstract Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics human in terms of synapse density expression patterns, well developmental, motor, cognitive abilities. Peripheral also biomarker Alzheimer’s disease schizophrenia, with nasal administration snippet peptide NAP (enhancing endogenous activity) to partial functional protection at cellular, animal clinical settings. Here, novel formulation effective delivery provided superior penetration capabilities. Also are methods treating pertinent implications such autism, impairments, olfactory deficits, muscle strength using mouse. Results showed dramatically specific increase brain/body bioavailability new formulation, without breaching blood barrier. Additional findings included improvements daily intranasal treatments NAP, behavioral structural levels, diffusion tensor imaging (DTI), translatable practice. Significant effects on hippocampal cerebral cortical presynaptic Slc17a7 encoding vesicular excitatory glutamate transporter 1 (VGLUT1) were observed RNA immunohistochemical explaining DTI results. These tie first time reduction glutamatergic synapses autism/Alzheimer’s/schizophrenia-linked deficiency coupled amelioration (CP201).