Scientists at Weill Cornell Medicine have made an exciting discovery that could lead to new treatments for diseases like Alzheimer’s and frontotemporal dementia.
They found that harmful molecules called free radicals, made in a specific part of certain brain cells, may be a major reason why these diseases develop. The study was published in the journal Nature Metabolism.
Free radicals are also known as reactive oxygen species (ROS). They are created by mitochondria, which are small parts of cells that make energy from food. Normally, small amounts of ROS help cells work properly. But too much ROS can damage cells and cause inflammation.
For years, scientists have tried using antioxidants to block ROS and prevent brain damage. But these treatments didn’t work well in clinical trials. Dr. Adam Orr and Dr. Anna Orr, who led this new study, think that’s because antioxidants didn’t stop ROS at the exact place they were being made or were not targeted enough.
To solve this problem, Dr. Adam Orr developed a new way to search for drugs that could block harmful ROS right where they are produced, without hurting other important cell functions. Using this system, they found a group of compounds called S3QELs (pronounced “sequels”) that seemed promising.
The researchers discovered that one part of mitochondria, called Complex III, is a major source of harmful ROS. But the surprising part was that this ROS wasn’t coming from neurons, the main brain cells. Instead, it was coming from astrocytes, which are helper cells in the brain that support and protect neurons.
In their experiments, when the scientists gave brain cells the S3QEL compounds, they saw that neurons were protected — but only when astrocytes were also present. This showed that the ROS from astrocytes was playing a big role in the damage.
When astrocytes were exposed to disease triggers like inflammation or Alzheimer’s-related proteins such as amyloid-beta, they started making a lot more ROS. The S3QELs blocked this extra ROS, while other treatments did not.
Further research showed that ROS from astrocytes changed certain important proteins, which then caused thousands of genes to behave differently. These changes were tied to inflammation and brain diseases like dementia.
The team tested their findings in mice that were genetically engineered to have frontotemporal dementia. After receiving S3QEL treatment, the mice had less brain inflammation, fewer signs of disease, and even lived longer. Importantly, the treatment worked even when given after symptoms had already started.
Dr. Anna Orr explained that these benefits were likely due to the treatment’s very specific way of blocking the harmful ROS without affecting healthy brain functions. The treatment also caused no major side effects.
Now, the researchers are working to improve the S3QEL compounds and are studying how certain genes might increase or decrease dementia risk by affecting ROS production. They are partnering with chemist Dr. Subhash Sinha at Weill Cornell to develop even better treatments.
This discovery is changing how scientists think about free radicals in the brain. It shows that stopping ROS at the right place and time could be the key to preventing or slowing brain diseases. It also opens the door to new treatments that protect the brain by focusing on the cells that support it.
If you care about dementia, please read studies that eating apples and tea could keep dementia at bay, and Olive oil: a daily dose for better brain health.
For more health information, please see recent studies what you eat together may affect your dementia risk, and time-restricted eating: a simple way to fight aging and cancer.
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