Alzheimer’s & Circadian Rhythm: Brain Health Reset?

Blocking Internal Clock Protein Shows Promise in Limiting Alzheimer’s Progression

A groundbreaking new study suggests that disrupting the interaction between the body’s internal clock and the brain could offer a novel therapeutic avenue for slowing the progression of Alzheimer’s disease. Research published this week in Nature Aging details how inhibiting a specific protein impacts the progress of the disease in mouse models.

Researchers at Washington University School of Medicine in St. louis (WashU Medicine) have identified a potential target for future Alzheimer’s treatments: the REV-ERBα protein. The study, led by Erik Musiek, MD, PhD, and first author Jiyeon Lee, PhD, demonstrates that blocking this protein can lower levels of tau, a toxic protein heavily implicated in alzheimer’s pathology, and reduce damage to brain tissue.

The Circadian system and Brain Health

The research team’s investigation centers on the circadian system, the body’s natural 24-hour cycle that regulates sleep, metabolism, and other vital functions. While the role of REV-ERBα in regulating these rhythms has been established in other tissues, its impact on brain health has been less understood.The protein influences levels of nicotinamide adenine dinucleotide (NAD+), a crucial molecule for metabolism, energy production, and DNA repair.

Declining NAD+ levels are strongly correlated with both brain aging and the onset of neurodegenerative conditions. “Many over-the-counter supplements aim to raise NAD+ as a strategy to slow aging and promote cellular health,” highlighting the growing recognition of this molecule’s importance.

Did you know? – Alzheimer’s disease is a progressive brain disorder that gradually destroys memory and thinking skills,and there is currently no cure.

Targeting REV-ERBα Boosts NAD+ Levels

To understand REV-ERBα’s role in Alzheimer’s, the researchers genetically deleted the protein in two groups of mice. One group experienced the deletion throughout the body, while the other had it removed specifically in astrocytes – supportive cells that are a major component of the central nervous system. In both instances, NAD+ levels rose substantially.

this finding suggests that eliminating REV-ERBα in astrocytes directly increases NAD+ in the brain, opening a potential pathway for future treatments. “The results suggest that eliminating REV-ERBα in astrocytes directly boosts NAD+ in the brain,” according to the study.

Pro tip: – Astrocytes provide essential support to neurons, maintaining the brain’s chemical balance and supplying nutrients. Their role in neurodegenerative diseases is increasingly recognized.

Drug Treatment Offers Protection Against Tau Pathology

Further experimentation involved blocking REV-ERBα using both genetic methods and a novel drug already showing promise in studies related to amyloid-β and Parkinson’s disease. This approach not only increased NAD+ levels but also protected the mice from brain damage associated with tau. Tau aggregates are known to disrupt brain function and are a hallmark of neurodegenerative diseases like Alzheimer’s.

The researchers found that manipulating the body’s internal clock – specifically by inhibiting REV-ERBα – could offer a new stra

Reader question: – How might disruptions to our daily routines, like shift work or jet lag, impact the risk of developing neurodegenerative diseases?

Why: The study aimed to find a new way to slow down Alzheimer’s disease progression by targeting the connection between the body’s internal clock and brain health. Researchers focused on the REV-ERBα protein and its influence on NAD+ levels, which are crucial for brain function.

Who: The research was conducted by a team at Washington University School of Medicine in St.Louis, led by Erik Musiek, MD, PhD, and first author Jiyeon Lee, PhD. The study involved experiments on mouse models.

What: The study discovered that blocking the REV