Depletion of Normal BRCA1 Protein in Neurons Linked to Alzheimer’s Disease; Non-Mutated BRCA1 Required for Normal Learning & Memory; First-Ever Such Results Reported by Gladstone Institutes

Researchers from the Gladstone Institutes in San Francisco have shown, for the first time, that the unmutated BRCA1 (breast cancer 1) protein is required for normal learning and memory and is depleted by Alzheimer’s disease. BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. The new study, published online today (November 30, 2015) in an open-access article in Nature Communications, demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 protein in neurons and that BRCA1 depletion can cause cognitive deficits. The article is titled ““DNA Repair Factor BRCA1 Depletion Occurs in Alzheimer Brains and Impairs Cognitive Function in Mice.” “BRCA1 has so far been studied primarily in dividing (multiplying) cells and in cancer, which is characterized by abnormal increases in cell numbers,” says first author Elsa Suberbielle, Ph.D., a research scientist at the Gladstone Institutes. “We were therefore surprised to find that it also plays important roles in neurons, which don’t divide, and in a neurodegenerative disorder [Alzheimer’s disease] that is characterized by a loss of these brain cells.” In dividing cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances in the absence of cell division, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that, in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions. To test this idea, the scientists experimentally reduced BRCA1 levels in the neurons of mice.
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