Saturday, February 17, 2018

Breast cancer gene BRCA1 in the brain may be a factor in Alzheimer’s


brca1 gene

American researchers have shown for the first time that low levels of BRCA1 protein in the brain may be a factor in Alzheimer's disease. BRCA1 is a key protein known for DNA repair. However, their mutated form increases the risk of breast and ovarian cancers.

The study published in Nature Communications and conducted by the researchers from the nonprofit Gladstone Institutes in San Francisco, CA, and the University of California-San Francisco (UCSF) illustrates that Alzheimer's is associated with a depletion of BRCA1 in neurons and that BRCA1 depletion can result in cognitive deficits. [Read more Eating sweet food forms memory of the meal – findings could encourage novel treatment for obesity]

"It's extremely interesting that one molecule can be critically involved in two apparently opposing conditions: cancer, in which too many cells are born and neurodegenerative disease, in which too many brain cells die off,” says senior author Lennart Mucke, a professor of neuroscience with roles in both organizations. [Read more Exposure to environmental toxin may increase risk of Alzheimer's]

When BRCA1 gene was discovered over 20 years ago, it was a breakthrough in cancer research. The discovery led to a blood test to identify inherited mutations linked to breast and ovarian cancers. Most recent estimate suggests that among women, who inherit a harmful BRCA1 mutation, 55 to 65 percent will develop breast cancer and 39 percent will develop ovarian cancer by the age of 70.

As mentioned earlier, BRCA1 plays an important role in DNA repair. Inside cells, DNA remains as a double helix containing 2 strands, like a twisted ladder. Repair protein BRCA1 fixes the strands if a break occurs once in a while. Broken strands that are not repaired normally trigger cell suicide.

Some scientists believe that defects in DNA repair may contribute to neurological disorders like Alzheimer’s. Alzheimer’s disease is known to cause death of brain cells. One of the hallmarks of the disease is build-up of beta amyloid proteins in and around brain cells. It is not clear whether the beta-amyloid proteins are responsible for the death of brain cells.

The researchers found reduced levels of BRCA1 protein, but not other DNA repair proteins, in post-mortem brains of Alzheimer's patients and also in the mice brains which were bred to develop a type of Alzheimer’s. [Read more What Is Celiac Disease And How Do You Treat It?]

When the BRCA1 gene in parts of the brains of healthy mice was knocked out, it expedited increased breaks in DNA and various neurological damages.

The scientists also experimentally reduced BRCA1 levels in the neurons of mice. The reduction of BRCA1 caused the mice to develop cognitive impairment.

The researchers were able to reduce the levels of BRCA1 by adding amyloid protein precursor molecules to brain cells growing in culture.

Increased DNA damage in brain cells that leads to dementia is the result of lower levels of BRCA1 protein caused by accumulation of faulty amyloid protein in the brain.


"The functions of BRCA1 in the brain remain to be fully elucidated, but our findings suggest that it may play an important role in supporting critical brain functions in both health and disease," concluded Professor Mucke.

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