Reactive Astrocytes as Drug Target in Alzheimer’s Disease

<jats:p>Alzheimer’s disease is a neurodegenerative disease characterized by deposition of extracellular amyloid-<jats:italic>β</jats:italic>, intracellular neurofibrillary tangles, and loss of cortical neurons. However, the mechanism underlying neurodegeneration in Alzheimer’s disease (AD) remains to be explored. Many of the researches on AD have been primarily focused on neuronal changes. Current research, however, broadens to give emphasis on the importance of nonneuronal cells, such as astrocytes. Astrocytes play fundamental roles in several cerebral functions and their dysfunctions promote neurodegeneration and, eventually, retraction of neuronal synapses, which leads to cognitive deficits found in AD. Astrocytes become reactive as a result of deposition of A<jats:italic>β</jats:italic>, which in turn have detrimental consequences, including decreased glutamate uptake due to reduced expression of uptake transporters, altered energy metabolism, altered ion homeostasis (K<jats:sup>+</jats:sup>and Ca<jats:sup>+</jats:sup>), increased tonic inhibition, and increased release of cytokines and inflammatory mediators. In this review, recent insights on the involvement of, tonic inhibition, astrocytic glutamate transporters and aquaporin in the pathogenesis of Alzheimer’s disease are provided. Compounds which increase expression of GLT1 have showed efficacy for AD in preclinical studies. Tonic inhibition mediated by GABA could also be a promising target and drugs that block the GABA synthesizing enzyme, MAO-B, have shown efficacy. However, there are contradictory evidences on the role of AQP4 in AD.</jats:p>