The role of GluA 1 in central nervous system disorders

In the brain, the four subunits of the a-amino3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, glutamate A 1 (GluA 1), GluA 2, GluA 3, and GluA 4 form functionally different tetramers. Of these, GluA 1 is very important. It forms calcium-permeable (without GluA 2) AMPA receptors and induces the trafficking and integration of AMPA receptors within synaptic membranes. Increased GluA 1 expression and their phosphorylation are common mechanisms for the treatment of Alzheimer's disease, schizophrenia, depression, and chronic drug addiction. Moreover, GluA 1 is also involved in pain and epilepsy. Increased phosphorylation of serine 831 in the GluA 1 receptor is a mechanism necessary to alleviate Alzheimer's disease and depression. GluA 1 -/-knockout mice are used as a model of schizophrenia. A decrease in the total cell AMPA receptor currents and phosphorylation of serine 845 of GluA 1 is observed in chronic drug addiction. Increased expression of GluA 1 causes pain and is involved in epilepsy. GluA 1 -promoting AMPA receptor potentiators could be used to treat Alzheimer's disease and memory loss. In conclusion, GluA 1 agonists or antagonists might be effective in various disorders and conditions of the central nervous system that are based on GluA 1 status at the synaptic region.