Rev-erbs and Glia—Implications for Neurodegenerative Diseases

Recently, we described a role for the circadian clock protein and nuclear receptor Rev-erbα in regulating glial activation states in the brain. Deletion of Rev-erbα resulted in microglial as well as astrocytic activation, while a Rev-erbα agonist diminished the severity of lipopolysaccharide (LPS)-induced neuroinflammation. Concomitant with this glial activation is impaired neuronal health. These findings suggest that Rev-erb proteins may play critical roles in glial biology. Pertinent ideas such as the glial cell type of most importance, the translatability of these findings to human disease, and the effect of manipulating Rev-erbs in models of neurodegeneration, need to be explored further. In this commentary, we will address the potential role of Rev-erbs in neuroinflammation related to neurodegenerative diseases and speculate on Rev-erbs as potential therapeutic targets for these conditions.