Neuroinflammation and regulation of glial glutamate uptake in neurological disorders.
Oxidative stress, neuroinflammation, and excitotoxicity are frequently considered distinct but common hallmarks of several neurological disorders, including Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease. Although neuron degeneration and death are the ultimate consequences of these pathological processes, it is now widely accepted that alterations in the function of surrounding glial cells are key features in the progression of these diseases. In response to alteration in their local environment, microglia, commonly considered the resident immune cells of the nervous parenchyma, become activated and release a variety of soluble factors. Among these, proinflammatory cytokines and free radicals actively participate in the degenerative insults. In addition, excitotoxic neuronal damage resulting from excessive glutamate is frequently associated with impaired handling of extracellular glutamate by gliotic astrocytes. Although several research projects have focused on the biochemical mechanisms of the regulation of glial glutamate transporters, a relationship between activation of microglia and modulation of astrocytic glutamate uptake is now suggested. The aim of this review is to summarize and discuss the data showing an influence of inflammatory mediators and related free radicals on the expression and activity of glial glutamate transporters.
Tilleux
Sébastien
S
Laboratoire de Pharmacologie Expérimentale, Faculté de Médecine, Université catholique de Louvain, Brussels, Belgium.
Hermans
Emmanuel
E
D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009422:Nervous System Diseases / Q000150:complications* / Q000378:metabolism*; D009443:Neuritis / Q000209:etiology*; D009457:Neuroglia / Q000378:metabolism*
D005609:Free Radicals; D051246:Glucose Transport Proteins, Facilitative; D018836:Inflammation Mediators; D018698:Glutamic Acid