What if boosting neurons’ energy could delay Alzheimer’s and dementia?
Mitochondrial activity defects are suspected to play a role in neurodegenerative diseases. Yet until now, it has been difficult to determine whether this dysfunction is a cause of neuronal decline or merely a consequence of it. By stimulating these tiny cellular structures with a novel tool, researchers have managed to improve memory in animal models, opening the door to promising new therapeutic strategies.
Mitochondria are small organelles located inside our cells. Their job is simple but vital: to produce the energy cells need to function properly. The brain, as the body’s most energy-hungry organ, depends heavily on this supply. Neurons require a constant flow of energy from mitochondria to communicate with one another. When mitochondrial activity falters, neurons lack the fuel they need to operate effectively.
Neurodegenerative diseases are marked by the gradual deterioration of neuronal function, eventually leading to the death of brain cells. In conditions such as Alzheimer’s disease, neuronal degeneration – the stage that precedes cell death – is accompanied by reduced mitochondrial activity. What remained unclear, however, was whether these mitochondrial alterations actively drive the disease process or simply reflect damage already underway.
Without the proper tools, establishing a clear cause-and-effect relationship proved challenging.
Recently, in a study published in Nature Neuroscience, researchers from Inserm and the University of Bordeaux, in collaboration with scientists from the University of Moncton in Canada, developed an unprecedented method to selectively stimulate mitochondrial activity.
A specific and innovative tool
The researchers hypothesized that if stimulating mitochondria led to an improvement in symptoms in animal models, this would suggest that mitochondrial dysfunction occurs before neuronal loss in neurodegenerative conditions.
In earlier work, the team had identified the specific role of certain proteins known as G proteins. These proteins are responsible for transmitting information within cells and were shown to modulate mitochondrial activity in the brain.
Building on this foundation, the scientists engineered an artificial receptor called mitoDREADD-Gs. This receptor can directly activate G proteins within mitochondria, thereby enhancing mitochondrial activity in a targeted way.
This breakthrough provided, for the first time, a means to precisely control mitochondrial function inside neurons.
Mitochondria as a potential therapeutic target
When mitoDREADD-Gs was stimulated, mitochondrial activity increased, and memory improved in mouse models of dementia. According to Giovanni Marsicano, an Inserm research director and co-senior author of the study, this is the first research to demonstrate a direct causal link between mitochondrial dysfunction and symptoms associated with neurodegenerative diseases. The findings suggest that impaired mitochondrial activity may be at the origin of neuronal degeneration.
Étienne Hébert-Chatelain, professor at the University of Moncton and co-senior author, emphasized that while these results still need confirmation, they shed light on the essential role mitochondria play in maintaining healthy brain function. In the long term, the tool developed by the team could help identify the molecular and cellular mechanisms responsible for dementia and accelerate the discovery of effective therapeutic targets.
Luigi Bellocchio, Inserm researcher and co-senior author, explained that the next step is to evaluate the effects of sustained mitochondrial stimulation. The goal is to determine whether continuous activation could influence the symptoms of neurodegenerative diseases and, ultimately, delay or even halt neuronal loss if mitochondrial function is fully restored.
Taken together, these findings position mitochondria not just as passive victims of cellular decline, but as active players in the progression of brain disorders. By restoring the cell’s energy production system, scientists may be able to intervene earlier in the disease process – potentially slowing degeneration before irreversible damage occurs.
While much work remains to be done, this research marks a significant step forward. It suggests that targeting mitochondrial function could become a powerful strategy in the fight against neuronal degeneration and memory impairment. For patients and families affected by these devastating conditions, even a modest delay in progression would represent meaningful progress – and this innovative approach offers a new reason for cautious optimism.