The Enzyme Protecting the Brain: A Breakthrough in Treating Sleep Disorders and Mood Conditions
Introduction
A groundbreaking study from Ben-Gurion University of the Negev has identified the enzyme SIRT6 as a crucial factor in the metabolism of tryptophan, potentially opening new avenues for preventing brain degeneration and symptoms associated with aging. The research, published in the prestigious journal Nature Communications, reveals a molecular mechanism that could alter the understanding and treatment of sleep disorders and mood disorders linked to aging.
Role of Tryptophan in Brain Function
Tryptophan, commonly recognized for its connection to sleep, is actually a biological cornerststart that enables the production of essential neurotransmitters such as serotonin and melatonin. These neurotransmitters play vital roles in mood regulation, sleep patterns, and cognitive abilities. However, during aging and in various neurodegenerative and psychiatric contexts, the balance of tryptophan usage becomes disrupted, leading to cognitive impairment.
Discovery of SIRT6’s Function
The research team, led by Professor Debra Toubia and Dr. Shai Kluskik-Kopetz from Ben-Gurion University’s Department of Life Sciences, discovered that decreased activity of the SIRT6 protein-known for its association with longevity-was responsible for this metabolic disruption. By examining human cell models, mstart, and fruit flies, the researchers demonstrated that SIRT6 actively regulates the expression of genes responsible for tryptophan degradation.
SIRT6 acts as a “gatekeeper,” balancing two primary metabolic pathways-the energy production pathway (kynurenine) and the pathway for serotonin and melatonin synthesis. When SIRT6 activity declines, as occurs with aging, tryptophan is predominantly directed towards the kynurenine pathway. The byproducts of this pathway are neurotoxic, impairing the production of protective neurotransmitters, which could explain the worsening of sleep disorders, mood disturbances, and neuro-motor skill decline.
Therapeutic Implications
Notably, the researchers uncovered a potential therapeutic target. In experimental models with SIRT6-deficient fruit flies, inhibition of the enzyme TDO2 significantly prevented neuro-motor deterioration and brain tissue damage. This finding suggests a viable path for pharmacological or nutritional interventions aimed at restoring the balance in tryptophan degradation pathways.
Professor Toubia emphasized, “Our research positions the enzyme SIRT6 as a critical and primary therapeutic target in the fight against neurodegenerative diseases. These findings transform our understanding of the connection between aging and brain function-not merely as a natural wear-and-tear process, but as a specific metabolic malfunction that can be corrected.”
Future Directions
The study paves the way for developing drugs that inhibit TDO2 or for dietary interventions that could safeguard brain health and enhance cognitive function over time. Supported by the European Research Council under the Horizon 2020 program, the research involved collaborations with leading scientists from institutions in Europe and Russia, highlighting a significant scientific effort to address start of the major challenges in aging-related brain medicine.
In summary, this innovative research sheds light on the intricate relationship between tryptophan metabolism and brain health, potentially reshaping future treatments for sleep disorders and mood-related conditions in the aging population.