In a new study, researchers found a drug candidate previously shown to slow aging in brain cells may help reverse memory loss in inherited Alzheimer’s disease.
They also found that the drug, CMS121, works by changing how brain cells metabolize fatty molecules known as lipids.
The research was conducted by a team at Salk Institute.
Over the last few decades, the team has studied how a chemical called fisetin, found in fruits and vegetables, can improve memory and even prevent Alzheimer’s-like disease in mice.
More recently, the team synthesized different variants of fisetin and found that one, called CMS121, was especially effective at, improving the animals’ memory, and slowing the degeneration of brain cells.
In the new study, the team tested the effect of CMS121 on mice that develop the equivalent of Alzheimer’s disease.
They gave a subset of the mice daily doses of CMS121 beginning at 9 months old—the equivalent of middle age in people, and after the mice have already begun to show learning and memory problems.
The timing of the lab’s treatment is akin to how a patient who visits the doctor for cognitive problems might be treated.
After three months on CMS121, at 12 months old, the mice—both treated and untreated—were given a battery of memory and behavior tests.
In both types of tests, mice with Alzheimer’s-like disease that had received the drug performed equally well as healthy control animals, while untreated mice with the disease performed more poorly.
To better understand the impact of CMS121, the team compared the levels of different molecules within the brains of the three groups of mice.
They discovered that when it came to levels of lipids—fatty molecules that play key roles in cells throughout the body—mice with the disease had several differences compared to both healthy mice and those treated with CMS121.
In particular, the researchers pinpointed differences in something known as lipid peroxidation—the degradation of lipids that produces free radical molecules that can go on to cause cell damage.
Mice with Alzheimer’s-like disease had higher levels of lipid peroxidation than either healthy mice or those treated with CMS121.
The researchers then found that CMS121 lowered levels of a lipid-producing molecule called fatty acid synthetase (FASN), which, in turn, lowered levels of lipid peroxidation.
They also analyzed brain samples from human patients who had died of Alzheimer’s.
They found that the patients had higher amounts of the protein FASN than similarly aged controls who were cognitively healthy, which suggests FASN could be a drug target for treating Alzheimer’s disease.
The researchers hope other researchers will explore additional compounds that may treat Alzheimer’s by targeting FASN and lipid peroxidation.
One author of the study is Pamela Maher, a senior staff scientist.
The study is published in Redox Biology.
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