title: Overview of Glutamatergic Dysregulation in Central Pathologies.
abstract: As the major excitatory neurotransmitter in the mammalian central nervous system, glutamate plays a key role in many central pathologies, including gliomas, psychiatric, neurodevelopmental, and neurodegenerative disorders. Post-mortem and serological studies have implicated glutamatergic dysregulation in these pathologies, and pharmacological modulation of glutamate receptors and transporters has provided further validation for the involvement of glutamate. Furthermore, efforts from genetic, in vitro, and animal studies are actively elucidating the specific glutamatergic mechanisms that contribute to the aetiology of central pathologies. However, details regarding specific mechanisms remain sparse and progress in effectively modulating glutamate to alleviate symptoms or inhibit disease states has been relatively slow. In this report, we review what is currently known about glutamate signalling in central pathologies. We also discuss glutamate's mediating role in comorbidities, specifically cancer-induced bone pain and depression.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. raaphot@mcmaster.ca.
authors.forename: Tanya
authors.initials: T
authors.lastname: Miladinovic
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. nashedm@mcmaster.ca.
authors.forename: Mina G
authors.initials: MG
authors.lastname: Nashed
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. singhg@mcmaster.ca.
authors.forename: Gurmit
authors.initials: G
authors.lastname: Singh
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002493:Central Nervous System Diseases / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D017470:Receptors, Glutamate; D018698:Glutamic Acid
keywords: excitotoxicity; glutamate; glutamate dysregulation; neurodegenerative disease; psychiatric disorder