Ionotropic glutamate receptors & CNS disorders.
Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although aetilogy is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual's susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous CNS disorders. Specifically, I argue that our understanding of iGluRs has reached a critical turning point to permit, for the first time, a comprehensive re-evaluation of their role in the cause of disease. I illustrate this by highlighting how defects in AMPA receptor (AMPAR) trafficking are important to fragile X mental retardation and ectopic expression of kainate receptor (KAR) synapses contributes to the pathology of temporal lobe epilepsy. Finally, I discuss how parallel advances in studies of other neurotransmitter systems may allow pharmacologists to work towards a cure for many CNS disorders rather than developing drugs to treat their symptoms.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Québec, Canada. derek.bowie@mcgill.ca
Derek
D
Bowie
D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004827:Epilepsy / Q000188:drug therapy; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter