Translational medicine of the glutamate AMPA receptor

Proc Jpn Acad Ser B Phys Biol Sci. 2021;97(1):1-21. doi: 10.2183/pjab.97.001.

Abstract

Psychiatric and neurological disorders severely hamper patient's quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are essential structural units of neurotransmission, and neuropsychiatric disorders are considered as "synapse diseases". Thus, a translational approach with synaptic physiology is crucial to tackle these disorders. Among a variety of synapses, excitatory glutamatergic synapses play central roles in neuronal functions. The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a principal component of glutamatergic neurotransmission; therefore, it is considered to be a promising translational target. Here, we review the limitations of current diagnostics and therapeutics of neuropsychiatric disorders and advocate the urgent need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Furthermore, we introduce our recent translational approach to these disorders by targeting at AMPARs.

Keywords: AMPA receptor; PET probe; ednonerpic maleate; synapse; synaptic plasticity; translational medicine.

MeSH terms

  • Animals
  • Humans
  • Receptors, AMPA / metabolism*
  • Translational Research, Biomedical*

Substances

  • Receptors, AMPA