SLC1 glutamate transporters and diseases: psychiatric diseases and pathological pain

Curr Mol Pharmacol. 2013 Jul;6(2):66-73. doi: 10.2174/18744672113069990033.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Transport System ASC / metabolism*
  • Animals
  • Glutamate Plasma Membrane Transport Proteins / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Minor Histocompatibility Antigens
  • Mood Disorders / metabolism
  • Pain / metabolism
  • Schizophrenia / metabolism
  • Substance-Related Disorders / metabolism
  • Synaptic Transmission

Substances

  • Amino Acid Transport System ASC
  • Glutamate Plasma Membrane Transport Proteins
  • Minor Histocompatibility Antigens
  • SLC1A4 protein, human
  • SLC1A5 protein, human
  • Glutamic Acid