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Glutamate plays crucial roles in the physiology of the central nervous system as it can control many functions such as memory, learning, cognitive, emotional, endocrine and other visceral functions. In addition, glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. It has the potential to be involved in the pathogenesis of many CNS diseases either due to excessive release, reduced uptake or alteration of receptor functions. Growing evidence links glutamate excitotoxicity to various neurodegenerative diseases as cerebral ischemia, epilepsy, Alzheimer's disease, Parkinsons' disease and multiple sclerosis. In addition, several environmental pollutants result in excessive glutamatergic neurotransmission and may eventually lead to neurodegenerative diseases.