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In the canonical Notch signaling, the Notch ligand binding to its receptor results in the removal of the extracellular fraction, and then two protein hydrolysis by A disintegrin and metalloprotease (ADAM10/17) and subsequently by a -secretase, respectively, 233 results in the generation of the Notch active form, NICD (Notch intracellular domain)

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Glutamate action on N-methyl D-aspartate (NMDA) receptors, one of its ionotropic receptors, incites Ca +2 influx and Ca +2 -calmodulin-dependent activation of nitric oxide synthase (NOS) which then produces Nitric oxide (NO), the signal that sustains glutamate release [210]