Glucose metabolism has long been known to be disrupted in aging brains, especially in neurodegenerative conditions like Alzheimer’s and Parkinson’s. As researchers delve deeper into this field, they have identified an enzyme that plays a critical role in regulating glucose metabolism in the brain. In a groundbreaking discovery, a cancer drug has been found to potentially help treat early-stage Alzheimer’s by restoring function in the hippocampus of Alzheimer’s mouse models.
The enzyme in question is called indoleamine-2,3-dioxygenase 1, or IDO1, which has been found to regulate glucose metabolism changes in the brain that occur in conditions like Alzheimer’s disease (AD) and Parkinson’s disease (PD). By blocking IDO1 in an Alzheimer’s mouse model, researchers were able to preserve memory and cognition in the early stages of the disease. This discovery has paved the way for the potential use of an immunotherapy cancer drug to target this pathway and restore function in affected areas of the brain.
A recent study conducted by researchers from various prestigious institutions including Stanford University, Kyoto University, Princeton University, Salk Institute, and Penn State, focused on how an enzyme present in astrocytes affects neuron signaling in the hippocampus. This area of the brain is essential for memory and learning functions. The production of lactate, which fuels neurons, is regulated by the molecule kynurenine. IDO1 is responsible for converting the amino acid tryptophan to kynurenine, which has been linked to brain aging and neurodegenerative diseases.
The research team was initially studying the immune mechanisms underlying brain injury when they stumbled upon the inflammatory pathway associated with prostaglandin E2. This led them to investigate the metabolism of tryptophan into kynurenine and the role of IDO1 in this process. Contrary to their expectations, they found that IDO1 played a crucial role in astrocytes rather than immune cells. This shift in focus allowed them to zero in on astrocytes and their metabolic support of neurons, uncovering new insights into the mechanisms of Alzheimer’s disease.
The study revealed that IDO1 activity was primarily observed in astrocytes, not neurons, in mice models. The researchers hypothesized that amyloid beta and tau proteins, characteristic of Alzheimer’s disease, could increase IDO1 expression in astrocytes, leading to a disruption in glucose metabolism. Further experiments using a cancer immunotherapy drug that inhibited IDO1 activity demonstrated promising results, with improvements in memory in mouse models of Alzheimer’s disease.
The findings of this study have significant implications for the development of novel treatments for Alzheimer’s disease and other neurodegenerative conditions. Clinical trials involving metabolic interventions, such as the use of IDO1 inhibitors, could offer new hope for patients suffering from these debilitating diseases. As more research is conducted on patient-derived astrocytes and different neurological conditions, we may gain a better understanding of the role of glucose metabolism in neurodegenerative disorders. The future looks promising, with the possibility of utilizing metabolic interventions like metformin, ketogenic diets, or GLP-1 agonists to target impaired glucose metabolism in various neurological conditions.