Excessive glutamate causes an up-regulation of the multiple signaling pathways, including phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Akt/mammalian target of rapamycin (mTOR) protein, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2, and autophagy that are involved in neurodegenerative diseases pathophysiology. This evidence concerns the gene WNK2 and neurodegenerative disease.