REV-ERBα inhibition increases NAD+ and reduces tau in mice, study in Nature Aging
Disrupting communication between the brain and the body's biological clock may slow neurodegeneration in Alzheimer's models, according to a new study from the University of Washington School of Medicine, published in Nature Aging..
In the study, the researchers targeted a circadian protein called REV-ERBα. Inhibiting it increased NAD+ levels and reduced harmful tau protein accumulation in mice.
How does the brain know it's time to take a breath, that blood pressure has dropped, or that the body is fighting an infection? The key may lie in the connections between the biological clock and the brain. New research has examined what happens when you suppress the activity of a key circadian protein and how this affects brain health.
Erik Musiek, MD, PhD, professor of neurology and the Charlotte & Paul Hagemann Professor at WashU Medicine, along with principal investigator Jiyeon Lee, PhD, and their team, showed that blocking the protein's function in Alzheimer's model mice reduced tau accumulation and reduced neurodegeneration.
How REV-ERBα affects brain aging
REV-ERBα regulates the circadian rhythm of metabolism and inflammation. Although its role in the brain has not been extensively studied, studies in other tissues suggest that it influences levels of NAD+, a molecule essential for energy metabolism and DNA repair. NAD+ levels are closely linked to brain aging and neurodegeneration. Low levels have been linked to more rapid decline. Many over-the-counter supplements claim to increase NAD+ to slow aging.
Musik and his team genetically deleted REV-ERBα in all tissues in one group of mice, and in another group they deleted it only in astrocytes – central glial cells in the nervous system. In both cases, NAD+ levels increased. The findings indicate that deletion in astrocytes directly affects NAD+ in the brain, opening a research avenue for future treatments for neurodegeneration.
Pharmacological inhibition and neuroprotection in Alzheimer's models
The researchers found that inhibiting REV-ERBα – genetically and pharmacologically using an experimental molecule that has previously shown promise in amyloid-beta pathology and Parkinson's disease – increased NAD+ and protected against tauopathy (tau pathology). The result suggests a new therapeutic approach for the prevention and treatment of Alzheimer's disease.
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