Scientists at the Institute for Basic Science (IBS) in South Korea have made an important discovery that could help explain how Alzheimer’s disease leads to memory loss.
They found that an enzyme called SIRT2, previously not linked to Alzheimer’s, plays a major role in how brain support cells called astrocytes contribute to cognitive decline.
For a long time, astrocytes were thought to be simple helper cells that just supported neurons. But recent research has revealed that astrocytes are much more active in the brain’s day-to-day functioning.
In Alzheimer’s disease, these astrocytes become “reactive”—they change their behavior in response to harmful plaques made of amyloid-beta (Aβ), one of the main signs of the disease. In trying to clean up these plaques, astrocytes can actually make the situation worse.
Here’s how: astrocytes take in the Aβ plaques through a process called autophagy and then break them down using a chemical process called the urea cycle. While this might seem helpful, it creates too much of a brain chemical called GABA, which slows down brain activity.
Too much GABA interferes with memory and thinking. The process also releases hydrogen peroxide (H₂O₂), a harmful substance that damages brain cells and leads to further memory loss and brain shrinkage.
The research team, led by Director C. Justin Lee at the IBS Center for Cognition and Sociality, wanted to find out which enzymes were responsible for this excessive GABA production.
By using advanced tools like brain imaging and electrical measurements in brain cells, they found two enzymes—SIRT2 and ALDH1A1—that were active in producing too much GABA in astrocytes affected by Alzheimer’s.
The SIRT2 enzyme was especially active in Alzheimer’s mouse models and even in the brains of humans who had died from the disease.
When the scientists blocked the action of SIRT2 in the mouse models, they noticed some promising results: the mice had less GABA in their brains and showed improvements in short-term memory. However, long-term spatial memory didn’t improve, which raised new questions.
The researchers explained that SIRT2 acts in the final step of GABA production. By the time SIRT2 does its job, the cells have already made hydrogen peroxide. So even if you stop SIRT2 and reduce GABA, the harmful effects of hydrogen peroxide might still continue.
This finding is important because it shows that GABA and hydrogen peroxide cause different kinds of damage—and they can be studied separately. Previously, scientists used MAOB inhibitors to block both GABA and hydrogen peroxide production. But that made it hard to figure out which chemical was causing which effect.
Now, with the identification of SIRT2 and ALDH1A1 as “downstream” targets, researchers can try new treatments that only block GABA without affecting hydrogen peroxide. This gives them a clearer picture of how Alzheimer’s disease works and what can be done to stop it.
Lead researcher Mridula Bhalla, a postdoctoral fellow at IBS, noted that while the improvements in memory were only partial, the results still offer exciting new directions for treatment.
Director Lee added that SIRT2 might not be the perfect drug target on its own, but its discovery is a big step toward more precise therapies. By targeting specific enzymes in the disease process, scientists hope to develop new drugs that are more effective and cause fewer side effects.
In summary, this study doesn’t just point to a new player in Alzheimer’s disease—it also offers a new way of thinking about how the disease damages the brain. Instead of focusing only on neurons, we now know that astrocytes—and the enzymes they use—also play a crucial role.
This opens the door to smarter, more targeted treatments for memory loss in Alzheimer’s disease.
If you care about Alzheimer’s disease, please read studies that bad lifestyle habits can cause Alzheimer’s disease, and strawberries can be good defence against Alzheimer’s.
For more information about brain health, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
The research findings can be found in Molecular Neurodegeneration.
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