BRCA1 is well known. Its action on the brain is less so. According to a new study, this protein would promote memory disorders observed in Alzheimer’s disease.
In people’s minds, this protein is associated with breast cancer, possibly ovarian cancer. But BRCA1 is also involved in DNA repair. This role also links her to Alzheimer’s disease. This has just been demonstrated by a team from the Gladstone Institutes (San Francisco, California, United States). Its members publish in Nature Communications the results of research on mice and on the brains of deceased persons.
When cells divide, the BRCA1 protein is responsible for repairing the damage inflicted on DNA. In neurons, this process does not occur. In contrast, “double-stranded breaks” occur after intense brain activity. This is where BRCA1 comes in. The authors of this publication speculated that this phenomenon promotes learning and memorization. An imbalance in the expression of the protein would then disrupt these cognitive functions.
Under expressed from 65 to 75%
To test this hypothesis, the team used two groups of mice. In the first, the expression of BRCA1 in neurons was reduced. The second has not been modified.
Placed in a labyrinth, the animals had to swim to escape. By comparing swimming speed and the ability to find the exit, the researchers were able to observe a significant difference between the two groups. The mice producing less BRCA1 showed poorer performance, in particular with difficulty memorizing the way out of the labyrinth. The reduction of the BRCA1 factor leads to the accumulation of damage to DNA, which promotes the destruction of neurons, and causes learning and memory disorders.
These same disorders appear early in Alzheimer’s disease. The authors therefore studied the brains of deceased patients, in order to analyze the level of BRCA1 compared to normal brains. In people with the pathology, the protein is 65 to 75% less present. An alteration that had already been observed in another neurodegenerative disease, Huntington’s disease.
Handle in prevention
To better understand the links between Alzheimer’s and BRCA1, scientists first exposed cultured cells with beta-amyloid proteins. Result: they reduce the level of BRCA1, which suggests their key role in DNA repair, and its dysfunction in Alzheimer’s patients. The same phenomenon is observed in mice.
The team is now looking at ways to combat this reduction in BRCA1 levels in the brain. “Therapeutic manipulation of repair factors such as BRCA1 could ultimately be used to prevent neuronal damage and cognitive decline in patients with Alzheimer’s disease or people at risk of developing it,” explains Lennart Mucke, director of the Gladstone Institute for Neurological Diseases. By normalizing the levels or function of BRCA1, it would be possible to protect neurons from excessive DNA damage and prevent the deleterious processes that this can cause. “
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