Scientists identified a new key trigger in the development of dementia: free radicals coming from specific regions of the star-shaped brain support cells, known as astrocytes.
The discovery was led by researchers from Weill Cornell Medicine in New York, United States. This work suggests a fundamental change in treatment strategy, moving from eliminating toxic proteins in neurons to finding how to calm overactive brain support cells.
The research focused on the mitochondriathe tiny structures present in astrocytes and other cells that take nutrients from food and convert them into chemical energy.
According to the results of this trial, published in the scientific journal Nature Metabolism, an effective treatment for neurodegenerative disease It may not just be about removing waste, such as excess tau protein, from neurons, but rather calming the inflammation that allows damage to progress.
Scientists have identified a new key trigger in the development of dementia. Illustrative photo: Shutterstock.Although mitochondria create most of the energy needed for the body to function, they also release reactive oxygen species (ROS), molecules commonly known as free radicals. While ROS helps regulate essential cellular functions to normal levels, its excessive or untimely production can cause cellular damage.
In diseased astrocytes, external triggers, such as inflammatory molecules or amyloid beta proteins linked to Alzheimer’s, caused a specific site in the mitochondria to excessively produce ROS at the wrong time and place. Harmful free radicals emitted by astrocytes were found to activate genes known to drive brain inflammation.
S3QEL: a promising compound in the fight against dementia
The research team tested a compound called S3QEL in mice modeling frontotemporal dementia. These compounds were specifically designed to target the Complex III (CIII) pathway within the mitochondria, in hopes of reducing the production of harmful free radicals.
After administer S3QEL to micethe research team tried them for several months to look for key changes. They tested the mice’s behavior, movement and coordination to see if their symptoms improved.
The diseased mice, which previously showed abnormal curling of the legs when held by the tail (a reflex indicating poor motor control), reduced this symptom with the drug.
When the compound was administered, astrocytes were less activated, and inflammatory signals decreased throughout the brain. When the mice were humanely euthanized, the researchers found that The treated mice had lower inflammation markers in their brains and less activated microglia, which are the immune cells of the central nervous system.
The research team tested a compound called S3QEL in mice modeling frontotemporal dementia. Illustrative photo: Pexels.The team also reported a decrease in tau proteins linked to dementia. In healthy brain cells, tau protein helps stabilize internal structures; However, in cases of dementia, these break off and clump together into toxic tangles inside neurons, which eventually kills them. The treated mice had fewer of these toxic tau proteins.
In a separate cohort of mice that were not euthanized, diseased mice treated with S3QEL in their food They lived 17 to 20 percent longer than those who received the placebo. Additionally, the team also reported that mice taking the experimental treatment in their food lived longer than mice eating standard food without S3QEL.
Surprisingly, these beneficial effects appeared even when treatment began after dementia symptoms had already begun.
The doctor Adam Orrcorresponding author, commented that «the study really changed the way we think about free radicals and opened many new avenues of research.» Yes ok It will take years to develop and test a drug for human usethis work points to a future where dementia could be controlled using a specific medication that slows its devastating course.
