4E-BP2 deamidation significantly alters protein production in the brain and nervous system. It maintains the balance of protein production required for a healthy nervous system. Any imbalance in protein production in the brain and nervous system causes all neurodegenerative diseases. Discovering what causes 4E-BP2 deamidation only in neurons will make it possible to control this balance of protein production and cure neurodegenerative diseases such as memory loss, Alzheimer's, and Parkinson's. Alzheimer’s disease is caused by the absence of 4E-BP2 protein in the brain's neurons. This protein undergoes deamidation spontaneously only in the neurons and, in this way, controls the production of proteins in the neurons. This, in turn, determines whether or not Alzheimer’s and Parkinson’s disease start or progress. The purpose of this work is to discover the neurobiological mechanism that causes the deamidation reaction in the 4E-BP2 protein by performing immunoblotting in the retinal ganglia, the optic nerve, the dorsal root ganglia, the sciatic nerve, and the whole brain, extracted via dissection from 2-month-old, Wild-type male mice. The results showed that deamidation mainly occurs in the axons or axon-enriched regions of the optic nerve, the whole brain, and the sciatic nerve, confirming conclusively that axons are the critical factors behind the neurobiological mechanism of 4E-BP2 protein deamidation. The results confirm that they are also the reason why 4E-BP2 deamidation occurs only in neural tissue.

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localized mRNA translation is im-portant for the structural changes at synapses supporting brain plasticity consolidation. Sleep has been shown activate the translation mTOR pathway, via phosphorylation of 4E-BPs, during brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BPs phosphorylation at cortical and cerebellar synapses with Western Blot. Sleep significantly increased the conversion of 4E-BPs to its hyperphosphorylated form at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band dur-ing active exploration and in the theta to beta (4-30Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BPs hyperphosphorylation at synapses. Our results provide a link between EEG and mo-lecular markers of plasticity across wake and sleep.