Reactive astrocytes give neurons less support: implications for Alzheimer's disease

Astrocytes become activated in Alzheimer's disease (AD), contributing to and reinforcing an inflammatory cascade. It is proposed that by transforming from a basal to a reactive state, astrocytes neglect their neurosupportive functions, thus rendering neurons vulnerable to excitotoxicity and oxidative stress. This review considers 3 important astrocytic functions, that when disrupted, can affect neuronal metabolism. 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. Conditions under which these functions can be manipulated in vitro, as well as examples of possible loss of astrocytic function in AD, are discussed. It is proposed that the targeting of astrocytes with pharmacological agents that are specifically designed to return astrocytes to a quiescent phenotype could represent a fruitful new angle for the therapeutic treatment of AD and other neurodegenerative disorders.