[ALS and excitatory amino acid].

AMPA receptor, one of ionotropic glutamate receptors, has been proposed to play a critical role to initiate the neuronal death cascade in motor neuron disease by an increase of Ca2+ influx. There are at least two mechanisms to increase Ca2+ influx through Ca2+-permiable AMPA receptor: a decrease of RNA editing efficacy at the GluR2 Q/R site and a decrease of GluR2 level relative to AMPA receptor subunits. Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). On the other hand, relative low GluR2 level among AMPA receptor subunits seems to increase Ca2+ permeability of motor neurons in familial ALS (ALS1) linked to mutated cupper-zinc superoxide dismutase gene (SOD1). AMPA receptor-mediated mechanism does not seem to play any role in death of motor neurons in X-linked spinal and bulbar muscular atrophy (SBMA). From the molecular pathomechanism of sporadic ALS and ALS1, drugs which increase RNA editing efficacy at the GluR2 Q/R site could be a potent therapy for sporadic ALS, while AMPA receptor antagonists could prevent deterioration from ALS1.