The role of GluA1 in central nervous system disorders

Abstract

In the brain, the four subunits of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, glutamate A1 (GluA1), GluA2, GluA3, and GluA4 form functionally different tetramers. Of these, GluA1 is very important. It forms calcium-permeable (without GluA2) AMPA receptors and induces the trafficking and integration of AMPA receptors within synaptic membranes. Increased GluA1 expression and their phosphorylation are common mechanisms for the treatment of Alzheimer's disease, schizophrenia, depression, and chronic drug addiction. Moreover, GluA1 is also involved in pain and epilepsy. Increased phosphorylation of serine831 in the GluA1 receptor is a mechanism necessary to alleviate Alzheimer's disease and depression. GluA1-/- knockout mice are used as a model of schizophrenia. A decrease in the total cell AMPA receptor currents and phosphorylation of serine845 of GluA1 is observed in chronic drug addiction. Increased expression of GluA1 causes pain and is involved in epilepsy. GluA1-promoting AMPA receptor potentiators could be used to treat Alzheimer's disease and memory loss. In conclusion, GluA1 agonists or antagonists might be effective in various disorders and conditions of the central nervous system that are based on GluA1 status at the synaptic region.