Lilianne R. Mujica-Parodi, a distinguished figure in the field of metabolic neuroscience, has made groundbreaking discoveries regarding the mechanisms driving cognitive decline. Serving as the Baszucki Endowed Chair of Metabolic Neuroscience, Professor of Biomedical Engineering, and Director of the Laboratory for Computational Neurodiagnostics (LCNeuro) at the State University of New York at Stony Brook, Dr. Mujica-Parodi led a pivotal study that unravels critical insights into neuronal energy sources and their implications on aging brain networks.
The study highlights that neuronal insulin resistance, primarily driven by an Alzheimer's risk factor protein known as APOE, is a significant contributor to the aging of brain networks. Mujica-Parodi's research underscores the vital role played by the insulin-dependent glucose transporter GLUT4, which, while abundant in muscle and fat tissue, is present in only specific regions of the brain. This revelation about GLUT4 adds a new layer of understanding to how neurons access energy and how this process may falter with age.
Mujica-Parodi described neurons as capable of utilizing two types of fuel: glucose, derived from sugar, and ketones, derived from fatty acids. Her findings suggest that when neurons become insulin-resistant, they lose access to glucose but can still utilize ketones. This alternative pathway may provide a promising direction for preventing cognitive decline.
“When neurons become insulin-resistant, they lose the ability to access glucose as fuel, but not ketones. This means that ketones can function as a ‘back door’ to feeding neurons whose access to glucose would otherwise be blocked by insulin resistance.” — Lilianne R. Mujica-Parodi, PhD
The potential of ketones as an alternative brain fuel presents an intriguing avenue for future research and interventions aimed at mitigating cognitive decline. This is particularly relevant given the challenges associated with maintaining adequate energy supplies to the brain as it ages.
“Our study suggests that, while diminished access to energy is the driving mechanism, seen in the 40’s, eventually, the degenerative effects compound, thereby accelerating a process in the 60’s that sets the trajectory for a path that is harder to reverse.” — Lilianne R. Mujica-Parodi, PhD
Dr. Mujica-Parodi's analogy further illustrates the significance of early intervention in addressing these challenges. She likens the situation to a bustling city reliant on a steady supply of electricity; when power is lost, immediate restoration prevents lasting damage. However, prolonged outages lead to structural degradation that cannot be reversed simply by restoring power.
“Water systems stop working, causing pipes to freeze and burst. Buildings deteriorate without climate control, and infrastructure begins to crumble. By the time power is finally restored, significant structural damage has occurred that simply turning the electricity back on cannot fix.” — Lilianne R. Mujica-Parodi, PhD
These insights emphasize the importance of addressing energy deficiencies in brain networks at an early stage. Identifying neuronal insulin resistance and exploring metabolic interventions, such as ketogenic diets, could offer promising strategies for preserving cognitive health.
The study conducted by Dr. Mujica-Parodi underscores the need for further research into ketogenic diets and their potential role in long-term cognitive protection. As highlighted by Verna Porter, MD, more evidence is needed to determine if such dietary interventions can be reliably maintained and integrated into broader treatment regimens.
“More research is needed to confirm whether a ketogenic diet can consistently be maintained and offer long-term protection, particularly in individuals at risk for Alzheimer’s, and whether it can be effectively incorporated into a broader treatment regimen.” — Verna Porter, MD
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