Scientists at the Institute for Basic Science (IBS) in South Korea have discovered a new enzyme, called SIRT2, that may play a key role in the memory loss seen in Alzheimer’s disease.
The study, led by Director C. Justin Lee at the IBS Center for Cognition and Sociality, offers new insights into how certain brain cells called astrocytes can contribute to cognitive decline.
Astrocytes were once thought to be simple support cells in the brain. But more recent research has shown that they do much more than that. They interact closely with neurons and play active roles in how the brain works.
In Alzheimer’s disease, astrocytes become “reactive” in response to amyloid-beta (Aβ) plaques — sticky protein clumps that are a key feature of the disease. These reactive astrocytes attempt to clean up the plaques using a process called autophagy and break them down using a mechanism known as the urea cycle.
However, this cleanup process comes at a cost: it causes the astrocytes to produce too much of a brain chemical called GABA, which slows down brain activity and leads to memory problems. The process also creates hydrogen peroxide (H₂O₂), a harmful substance that can damage and kill brain cells.
The IBS research team wanted to understand what causes this overproduction of GABA, in hopes of finding a way to block it without disrupting other brain functions.
By studying brain tissues from both Alzheimer’s model mice and humans who had the disease, they identified two enzymes, SIRT2 and ALDH1A1, that are closely involved in the harmful production of GABA in reactive astrocytes.
SIRT2 was found in higher amounts in the astrocytes of both the Alzheimer’s mice and human brains. When the scientists blocked SIRT2 in the Alzheimer’s mice, they saw two important effects: GABA levels dropped, and short-term working memory improved. However, long-term spatial memory did not improve. This partial result was both exciting and puzzling.
One reason the memory improvement was limited may be due to H₂O₂, which is produced earlier in the GABA production process, before SIRT2 comes into play.
Even when SIRT2 was blocked, H₂O₂ continued to be made and may have continued harming brain cells. This suggests that while reducing GABA may help with memory, it does not stop the ongoing cell damage caused by H₂O₂.
This finding is still a breakthrough. Before this, scientists used drugs that blocked MAOB, an enzyme that stops the production of both GABA and H₂O₂. But this approach made it impossible to understand which chemical was responsible for which effects in Alzheimer’s.
Now, with SIRT2 and ALDH1A1 identified as downstream targets — meaning they act later in the process — scientists can selectively stop GABA production while still allowing H₂O₂ production. This lets researchers study the separate effects of each chemical, a crucial step in understanding how Alzheimer’s disease works.
Director C. Justin Lee explains that although SIRT2 may not be an ideal drug target, the discovery gives researchers new tools to investigate how astrocytes influence brain decline. The ability to selectively block certain harmful chemicals, like GABA, without affecting others could lead to more precise and safer treatments for Alzheimer’s.
In summary, this study doesn’t offer a cure yet, but it does provide an important piece of the puzzle. By uncovering the role of SIRT2 in GABA overproduction, scientists now have a clearer picture of how astrocytes contribute to memory loss in Alzheimer’s and how future therapies might better target specific parts of the disease process.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more information about brain health, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
The research findings can be found in Molecular Neurodegeneration.
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