Activated astrocytes: a therapeutic target in Alzheimer’s disease?

Abstract

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.

Keywords::

• glucose
• glutamate
• glutathione
• lactate
• neurodegeneration

Financial & competing interests disclosure

Megan Steele is supported by a PhD fellowship from Alzheimer’s Australia.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.