Excitatory amino acid receptors, excitotoxicity, and the human nervous system.

Abstract

Glutamate receptors continued to be the subject of intense investigation during 1992. It is clear that there is great structural and functional diversity within this receptor family, although the precise subunit structure of excitatory amino acid (EAA) receptors in specific neuronal groups within the human central nervous system remains to be determined. Molecular studies have shown the existence of five genes encoding N-methyl-D-aspartate receptor subunits that have specific anatomic profiles and differing functional properties. The chromosomal localization of several genes encoding EAA receptor subunits has been established and some of these represent candidate genes for clinical neurologic disorders. Further insights were gained into the functions of metabotropic receptors, and three distinct genes encoding glutamate transporters were cloned. The interaction between neurotrophic factors and EAA neurotransmitters is increasingly recognized. Excitotoxicity is considered to represent a final common pathway of neuronal injury in an ever-increasing range of neurologic disorders. The development of therapeutic agents has focused on methods for reducing excitotoxicity without interfering with EAA receptor activation.