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
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"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.
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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.
They are now testing whether increasing BRCA1 levels in
mouse models can prevent or reverse brain damage and cognitive skills. [Read
more একা খাওয়া আপনার স্বাস্থ্যের জন্য মারাত্মক ক্ষতিকর হতে পারে]
"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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