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Basic Science Seminars in Neurology
March 2001

Glutamate Transporters in Neurologic Disease

Author Affiliations

From the Department of Neurology, Johns Hopkins University, Baltimore, Md.

 

HASSAN M.FATHALLAH-SHAYKHMD

Arch Neurol. 2001;58(3):365-370. doi:10.1001/archneur.58.3.365

Glutamate is the primary excitatory amino acid neurotransmitter in the human brain. It is important in synaptic plasticity, learning, and development. Its activity at the synaptic cleft is carefully balanced by receptor inactivation and glutamate reuptake. When this balance is upset, excess glutamate can itself become neurotoxic.

The neurotoxic properties of glutamate were first demonstrated in 1957 by Lucas and Newhouse,1 who showed that systemic administration of glutamate to infant mice caused retinal degeneration. Over the last 4 decades, a direct correlation between the neuroexcitatory and neurotoxic properties of glutamate has been linked to activation of excitatory amino acid receptors.25 This overactivation leads to an enzymatic cascade of events ultimately resulting in cell death.

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