Researchers have uncovered a crucial piece of the puzzle behind memory loss in Alzheimer’s disease.
A team from the Institute for Basic Science (IBS) has identified an enzyme called SIRT2 that plays a key role in how brain cells called astrocytes contribute to cognitive decline.
Astrocytes, once thought to merely support neurons, are now known to play active roles in brain function.
In Alzheimer’s, these cells react to the presence of amyloid-beta plaques—sticky protein clumps that build up in the brain and are a hallmark of the disease.
While astrocytes attempt to clean up these plaques, they trigger a harmful process that leads to memory loss.
As they break down the plaques, astrocytes produce too much of a brain chemical called GABA, which usually calms brain activity.
In this case, the overproduction of GABA dampens brain function too much, leading to problems with memory and thinking.
This breakdown process also creates hydrogen peroxide (H2O2), a toxic substance that damages neurons and contributes to brain degeneration.
Led by Director C Justin Lee of the IBS Center for Cognition and Sociality, the research team aimed to find out which enzymes were responsible for this excess GABA production.
Using advanced lab techniques on mice and human brain samples, they discovered that two enzymes—SIRT2 and ALDH1A1—play a critical role in GABA overproduction in Alzheimer’s-affected brains.
The study, published in Molecular Neurodegeneration, showed that SIRT2 levels were significantly higher in both Alzheimer’s mouse models and in brain tissue from people who had died with the disease.
When the researchers blocked SIRT2 in the mice, they saw improvements in short-term memory and a reduction in GABA levels. However, this did not stop the production of hydrogen peroxide, which continues to damage brain cells even when GABA levels drop.
Lead researcher Mridula Bhalla noted that while short-term memory improved in treated mice, spatial memory did not, suggesting that halting GABA alone isn’t enough to fully reverse the disease’s effects.
Still, the discovery is significant. By identifying SIRT2 and ALDH1A1 as enzymes further down the chain from another target called MAOB, scientists can now focus on more precise ways to reduce GABA without interfering with other brain functions or affecting hydrogen peroxide levels.
This breakthrough offers a clearer view of how different processes contribute to Alzheimer’s and opens the door to more targeted treatments that could slow or prevent memory loss in the future.
While SIRT2 may not be the perfect drug target, it marks a major step forward in understanding and eventually treating this devastating disease.
If you care about brain health, 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.
Source: KSR.
