The molecular activity of cells to their environment is synchronized by the circadian clock. The "core clock" of the circadian system is made up of a group of proteins that autonomously activate and repress each other. BMAL1, one of the activating core clock proteins, is critical for maintaining circadian rhythm and for controlling oxidative stress, normal aging and cognitive ability.
In this issue of the Journal of Clinical Investigation
, Erik Musiek and colleagues at Washington University School of Medicine asked whether BMAL1 and the rest of the core clock contribute to the maintenance of healthy neurons. Using Bmal1
-deficient mice, the authors found that as these mice aged activated astrocytes began to accumulate, a hallmark of active inflammation and damage. Bmal1
-deficient mice also displayed localized degeneration of neuronal cells and a loss of functional connectivity, as measured by blood flow.
The researchers found that BMAL1 and the other activating core clock proteins regulate important redox proteins that prevent damage caused by oxidative stress. In an accompanying commentary, Colleen McClung from the University of Pittsburgh noted that the activating circadian core clock proteins could be explored as targets for future therapies for neurodegenerative diseases.