Ionotropic Glutamate Receptors and their Role in Neurological Diseases

Glutamate is extensively and relatively uniformly distributed in the central nervous system (CNS) and its effects mediated by two distinct groups of receptors including Ionotropic and metabotropic glutamate receptors. Concentration of glutamate in the nervous system is much higher than in other tissues. Glutamate receptors play an important role in synaptic transmission, neural plasticity and neural development. Although glutamate has various neural physiological effects, it is a strong neurotoxin and high concentration of glutamate in synaptic milieu and extra cellular space plays a critical role in neurodegenerative diseases like ischemia, acute neural trauma and many other CNS disorders. Selective ligands for glutamate receptors have made considerable advances in the identification of the physiological and pathological roles of these receptors in the nervous system. Furthermore, advances in animal models of neurodegenerative disorders have lead to the application of many glutamatergic compounds in clinical studies. These compounds consist of ionotropic glutamate receptor antagonists that examined in clinical tests for disorders including epilepsy, ischemic stroke, etc. The purpose of this review is to describe ionotropic glutamate receptors and their possible roles in excitotoxicity and nervous system disorders. Then we will discuss briefly about transporters for glutamate and their association in the pathology of CNS disorders. Finally, involvement of ionotropic glutamate receptors in neurological disorders including schizophrenia, Alzheimer's disease and epilepsy will be explained.