Scientists find how to reverse memory loss

Mitochondria, the tiny energy-producing structures inside cells, are essential for keeping our bodies, and especially our brains, functioning.

A new study, published in Nature Neuroscience by researchers from Inserm and the University of Bordeaux, in collaboration with the Université de Moncton in Canada, has, for the first time, demonstrated a direct causal link between mitochondrial dysfunction and the cognitive symptoms observed in neurodegenerative diseases.

Using a unique and innovative tool, the researchers successfully increased mitochondrial activity in animal models of neurodegenerative diseases.

When they did this, the animals showed improved memory, suggesting that targeting mitochondria could be a promising new therapeutic approach. Although the findings are still in an early stage, they represent a significant step toward understanding the role of mitochondria in brain health.

Mitochondria provide the energy cells need to function, and neurons depend heavily on this energy to communicate effectively. In neurodegenerative diseases like Alzheimer’s, brain cells gradually lose their function and die.



Improved symptoms



Researchers have observed that even before neurons die, mitochondrial activity is often impaired. However, until now, it was unclear whether mitochondrial dysfunction was a cause of the disease or simply a byproduct.

In this study, scientists developed a tool to stimulate mitochondrial activity temporarily. They reasoned that if boosting mitochondria improved symptoms, it would indicate that mitochondrial problems occur before neuron loss and may contribute directly to the disease process.

Building on earlier work showing the role of G proteins in controlling mitochondrial activity, the team created an artificial receptor called mitoDreadd-Gs.

This receptor activates G proteins directly inside mitochondria, increasing their activity. When mitoDreadd-Gs was activated in the brains of dementia mouse models, both mitochondrial function and memory performance returned to normal levels.



Stimulating mitochondrial activity



Giovanni Marsicano, Inserm research director and co-senior author, said the findings are the first to establish a cause-and-effect link between mitochondrial dysfunction and neurodegenerative symptoms.

This suggests that mitochondrial impairment could be a trigger for neuronal degeneration rather than just a secondary effect.

Étienne Hébert Chatelain, professor at the Université de Moncton and co-senior author, noted that the new tool could help uncover the molecular and cellular mechanisms that cause dementia, making it easier to develop targeted treatments.

Luigi Bellocchio, Inserm researcher and co-senior author, added that the next step will be to test the effects of continuously stimulating mitochondrial activity to see if it can reduce symptoms, delay neuron loss, or even prevent it if activity is restored early enough.

This study opens an exciting new chapter in neurodegenerative disease research by identifying mitochondria as a potential root cause of cognitive decline. The creation of mitoDreadd-Gs provides a powerful experimental tool to test therapies aimed at restoring mitochondrial function.

If these findings can be replicated and translated into human studies, they could lead to treatments that address the underlying energy deficits in the brain, potentially slowing or halting diseases like Alzheimer’s at an earlier stage.

*The study is published in Nature Neuroscience.