AMPA receptor mediated excitotoxicity in ALS: pathophysiology and neuropharmacology

The term excitotoxicity was coined for the overstimulation of neurons via glutamate receptor channels. AMPA-type glutamate receptors (AMPA-R) are the most abundant excitatory transmitter receptors of the central nervous system. They play a major role in the cascade of cell damage in neurodegenerative diseases like amyotrophic lateral sclerosis. Neurons that are vulnerable to excitotoxicity express specific subtypes of AMPA-R as defined by the combination of subunits, by alternative splicing, and by nuclear editing of subunit mRNAs. The investigation of the neurophysiological properties of specific AMPA-R allows…