Activated astrocytes: a therapeutic target in Alzheimer's disease?
Astrocytes become activated in Alzheimer's disease, contributing to and reinforcing an inflammatory cascade. A large body of evidence suggests that by transforming from a basal to a reactive state, astrocytes neglect their neurosupportive functions, thus rendering neurons vulnerable to neurotoxins, including proinflammatory cytokines and reactive oxygen species. This review highlights three important astrocytic functions that may be impaired in neurodegenerative diseases such as Alzheimer's disease. These are: the uptake of glucose and release of lactate; the uptake of glutamate and release of glutamine; and the uptake of glutathione precursors and release of glutathione. Astrocytes could become promising targets of therapeutic intervention for Alzheimer's disease, if these compromised functions can be normalized with pharmacological agents that are specifically designed to return astrocytes to a quiescent phenotype or to supplement any factors that activated astrocytes fail to produce.
Fuller
Stacey
S
Department of Pharmacology, School of Medicine, University of Western Sydney, Campbelltown, NSW 1797, Australia. 16115024@student.uws.edu.au
Münch
Gerald
G
Steele
Megan
M
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006801:Humans