Link Between Circadian Clock Protein and Brain Aging: Implications for Neurodegenerative Diseases

Recent research from Washington University in St. Louis has highlighted a significant connection between the body's circadian clock and brain health, revealing that targeting specific circadian proteins may reduce the risk of neurodegeneration. A study published in Nature Aging shows that inhibiting the circadian clock protein REV-ERBα can elevate levels of nicotinamide adenine dinucleotide (NAD+), a molecule essential for cell metabolism, DNA repair, and overall brain function. Lower NAD+ levels have been associated with increased brain aging and neurodegenerative diseases such as Alzheimer's.

In experiments with mouse models of Alzheimer's disease, researchers genetically suppressed REV-ERBα across various tissues and specifically in astrocytes—glial cells crucial for brain health. Both approaches resulted in heightened NAD+ levels, indicating that REV-ERBα plays a direct role in regulating this vital molecule within the brain. Notably, the suppression of REV-ERBα also led to a decrease in tau protein accumulation, which is responsible for toxic brain protein aggregation in neurodegenerative disorders.

The team tested a novel drug that inhibits REV-ERBα and observed promising outcomes: mice treated with this compound exhibited increased NAD+ levels and were protected against tau pathology. These findings suggest a potential therapeutic pathway for diseases like Alzheimer’s, focusing on the modulatory effects of circadian proteins on brain aging and neurodegeneration.

This research underscores the importance of the circadian system in maintaining brain health and opens new avenues for treating neurodegenerative conditions by targeting molecular regulators like REV-ERBα. Further studies could pave the way for innovative therapies aimed at slowing or preventing the progression of neurodegenerative diseases, thus improving quality of life and cognitive longevity.

Source: https://medicalxpress.com/news/2025-10-circadian-clock-protein-linked-brain.html