title: Activated astroglia during chronic inflammation in Alzheimer's disease--do they neglect their neurosupportive roles?
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder, characterized histopathologically by the extracellular deposition of beta-amyloid peptide in senile plaques, as well as intracellular neurofibrillary tangles (NFT) of hyperphosphorylated tau protein, extensive neuronal loss and synaptic changes in the hippocampus and cerebral cortex. In addition, the AD brain shows chronic inflammation characterized by an abundance of reactive astrocytes and activated microglia. In the healthy brain, astrocytes provide essential services for brain homeostasis and neuronal function, including metabolic support for neurons in the form of lactate, glutamate uptake and conversion into glutamine, and synthesis of glutathione and its precursors. In AD, a large body of evidence now suggests that by transforming from a basal to a reactive state, astrocytes neglect their neurosupportive functions, thus rendering neurons vulnerable to neurotoxins including pro-inflammatory cytokines and reactive oxygen species. This review will explain the normal functions of astrocytes, and how these cells might be activated to turn into inflammatory cells, actively contributing to neurodegeneration and neglecting their neurosupportive roles ("neuro-neglect hypothesis"). Furthermore, it is proposed that astrocytes might be promising target 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 supplement factors which activated astrocytes lack to produce.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Western Sydney, Campbelltown, Australia.
authors.forename: Stacey
authors.initials: S
authors.lastname: Fuller
authors.forename: Megan
authors.initials: M
authors.lastname: Steele
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000975:Antioxidants / Q000627:therapeutic use; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008959:Models, Neurological; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018698:Glutamic Acid; D005978:Glutathione