Ketone bodies are produced by the body during fasting and low glucose availability, serving as an alternative energy source for cells. Recent research by Buck Institute scientists has uncovered a direct molecular mechanism for the regulation of misfolded proteins in the brain, suggesting ketone bodies play a significant role in maintaining brain health.
The study found that β-hydroxybutyrate (βHB), a primary component of ketone bodies, interacts directly with misfolded proteins in the brain, altering their solubility and structure to facilitate clearance through autophagy. This process is crucial for removing damaged proteins, which can contribute to neurodegenerative diseases such as Alzheimer’s.
In mouse models, ketone ester treatment resulted in the clearance of insoluble proteins, whereas pathological aggregation was observed without treatment. The researchers also studied nematode worms genetically modified to express human amyloid beta, demonstrating a significant impact on protein solubility and recovery from paralysis.
The discovery highlights a novel form of metabolic regulation of protein quality control, where ketone bodies interact with damaged proteins directly. This finding has implications for therapeutic development in aging and neurodegenerative diseases. The researchers are now exploring the potential applications of this mechanism in treating brain health disorders outside the brain, such as in the gut.
Source: https://www.genengnews.com/topics/translational-medicine/ketone-body-role-in-regulating-misfolded-proteins-may-inform-strategies-targeting-aging-alzheimers-disease