Translational enhancers of EAAT2: therapeutic implications for neurodegenerative disease

J Clin Invest. 2014 Mar;124(3):964-7. doi: 10.1172/JCI74608. Epub 2014 Feb 24.

Abstract

Glutamate excitotoxicity contributes to the neuronal injury and death associated with many neurodegenerative diseases. The glutamate transporter EAAT2, which is primarily localized on astrocytic processes, facilitates glutamate clearance from synapses, thus preventing neuronal damage. In this issue of the JCI, Kong et al. characterize a compound that upregulates EAAT2 translation, thereby increasing glutamate uptake by glial cells. Furthermore, this strategy for alleviating excitotoxicity was found to be beneficial in mouse models of both amyotrophic lateral sclerosis (ALS) and epilepsy, suggesting that future development in this chemical series may lead to much-needed treatments for these disorders.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Comment

MeSH terms

  • Animals
  • Excitatory Amino Acid Transporter 2 / genetics*
  • Female
  • Male
  • Neuroprotective Agents / pharmacology*
  • Protein Biosynthesis / drug effects*
  • Pyridazines / pharmacology*
  • Pyridines / pharmacology*

Substances

  • Excitatory Amino Acid Transporter 2
  • LDN-OSU-0212320
  • Neuroprotective Agents
  • Pyridazines
  • Pyridines