SLC1 Glutamate Transporters and Diseases: Psychiatric Diseases and Pathological Pain
Takayuki Nakagawa and Shuji Kaneko
Affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Keywords: Astrocyte, drug addiction, EAAT1, EAAT2, glutamate transporter, mood disorders, pathological pain, schizophrenia.
The solute carrier family 1 (SLC1) consists of two neutral amino acid transporters and five high-affinity excitatory
amino acid transporters (EAAT1-5). EAATs are expressed in glial cells (EAAT1/GLAST and EAAT2/GLT-1), neurons
(EAAT3/EAAC1 and EAAT4), and the retina (EAAT5), where they precisely regulate extracellular glutamate levels
at both synaptic and extrasynaptic sites. EAATs play essential roles in the maintenance of normal excitatory synaptic
transmission, protection of neurons from the excitotoxic action of excessive glutamate, and regulation of glutamatemediated
neuroplasticity. Therefore, dysfunction of EAATs can cause abnormal excitatory synaptic transmission, neuronal
excitotoxicity, and the exaggeration of neuroplasticity-based events. EAAT dysfunction has been implicated in a variety
of neurodegenerative and neurological diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s
disease, ischemia, and epilepsy. Recent evidence suggests that abnormalities of EAATs contribute to the pathogenesis
of psychiatric diseases and pathological pain. The present review will briefly discuss novel findings on the roles of
EAATs in the pathogenesis of psychiatric diseases such as schizophrenia, mood disorders, and drug dependence/
addiction, and pathological pain, as well as the potential of EAATs as therapeutic targets.
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