Study Links Mitochondrial Dysfunction to Cognitive Decline in Neurodegenerative Diseases

Recent research has uncovered a significant connection between mitochondrial dysfunction and cognitive symptoms prevalent in neurodegenerative diseases. Published in Nature Neuroscience, this groundbreaking study was conducted by a team from Inserm and the University of Bordeaux, in collaboration with researchers from the Université de Moncton in Canada.

Mitochondria, the organelles responsible for energy production within cells, have long been recognized for their essential role in cellular function, particularly in energy-demanding organs like the brain. Neurons depend heavily on the energy generated by mitochondria to communicate effectively. When mitochondrial function is compromised, it adversely affects neuronal activity, contributing to cognitive decline.

The study highlights that neurodegenerative diseases, such as Alzheimer's, are characterized by deteriorating neuronal functions, culminating in cell death. Previous observations indicated that the degeneration of neurons aligns with decreased mitochondrial activity, but establishing a causal relationship has been challenging due to a lack of appropriate research tools.

In this innovative research, scientists developed a novel tool enabling the temporary enhancement of mitochondrial activity in animal models suffering from neurodegenerative diseases. The results indicated that stimulating mitochondrial function resulted in noticeable improvements in memory deficits, suggesting that mitochondrial impairment may precede neuronal loss.

The research team had previously identified the role of G proteins in modulating mitochondrial activity within the brain. In this current study, they successfully created an artificial receptor called mitoDREADD-Gs, which activates G proteins directly within mitochondria, leading to enhanced mitochondrial activity.

Upon stimulating the mitoDREADD-Gs in the brains of dementia-affected mice, researchers observed normalization of both mitochondrial function and memory performance. Giovanni Marsicano, a research director at Inserm, noted that this study marks a pivotal moment in establishing a cause-and-effect link between mitochondrial dysfunction and the cognitive symptoms associated with neurodegenerative diseases. The findings suggest that mitochondrial impairment may be a primary factor leading to neuronal degeneration.

Étienne Hébert Chatelain, a professor at the Université de Moncton, emphasized the potential of this research in understanding mitochondrial roles in brain health. The tool developed could facilitate the identification of molecular and cellular mechanisms underlying dementia, paving the way for effective therapeutic targets.

Moving forward, the research team aims to assess the effects of sustained mitochondrial stimulation to determine its impact on neurodegenerative disease symptoms, with hopes of delaying or even preventing neuronal loss through restored mitochondrial function.

For further details, refer to the full study in Nature Neuroscience and its DOI: 10.1038/s41593-025-02032-y.