Ketone Bodies: A Promising Link Between Metabolism, Mitochondrial Function, and Brain Health
An insightful study published in Cell Chemical Biology by researchers at the Buck Institute for Research on Aging has unveiled new roles for ketone bodies beyond their well-known function in energy production. The research focuses on the impact of these metabolites, particularly β-hydroxybutyrate, on brain function in the context of aging and Alzheimer’s disease.
Key findings from the study include:
- Direct Interaction with Misfolded Proteins: The ketone body β-hydroxybutyrate interacts directly with misfolded proteins, changing their solubility and structure to promote their clearance from the brain through autophagy.
- Enhanced Protein Quality Control: Ketone bodies and similar metabolites have significant effects on the proteome, improving protein quality control mechanisms within the brain.
- Experimental Validation in Animal Models: In animal models, feeding ketone esters to mice facilitated the clearance of insoluble proteins, preventing their pathological aggregation. In nematode models expressing human amyloid beta, ketone treatment restored mobility, indicating a reversal of protein-induced paralysis.
- Potential Therapeutic Avenue: These findings suggest that manipulating ketone body levels could be a powerful strategy for clearing damaged proteins from the brain, offering a potential therapeutic approach for tackling brain aging and neurodegenerative diseases.
This study introduces a novel connection between metabolism, ketone bodies, and aging, proposing that ketone bodies act as signaling molecules that influence protein homeostasis in the brain. The potential for these findings to inform future therapeutic strategies for brain health is significant, providing new opportunities for addressing neurodegenerative diseases.
Image Credits: Sid Madhavan, Buck Institute for Research on Aging
