Dysfunctional astrocytes as key players in the pathogenesis of central nervous system disorders.
Once considered little more than the glue that holds neurons in place, astrocytes are now becoming appreciated for the key roles they play in central nervous system functions. They supply neurons and oligodendrocytes with substrates for energy metabolism, control extracellular water and electrolyte homeostasis, regulate neurotransmitter release, modulate immune responses, produce trophic factors, and control synapse formation. Astrocytes express receptors for many neurotransmitters, peptides, hormones and cytokines, and show excitability based on intracellular Ca2+ variations. Evidence is mounting that alterations in astrocyte functionality play a crucial role in the pathogenesis of disorders with diverse properties, including migraine, epilepsy, leukodystrophies, inflammatory demyelinating diseases, infections, brain edema and metabolic disorders, metal intoxications, neurodegenerative disorders, and schizophrenia. Targeting astrocyte dysfunction may lead to new therapeutic strategies for these disorders.
De Keyser
Jacques
J
Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. j.h.a.de.keyser@neuro.umcg.nl
Mostert
Jop P
JP
Koch
Marcus W
MW
D001253:Astrocytes / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology*; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000378:metabolism / Q000503:physiopathology; D018792:Encephalitis, Viral / Q000378:metabolism / Q000503:physiopathology; D020260:Heavy Metal Poisoning, Nervous System / Q000378:metabolism / Q000503:physiopathology; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000378:metabolism / Q000503:physiopathology; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D006801:Humans