Protective BRCA1 protein levels are lower in the brains of individuals with Alzheimer’s. Nature Communications, 11/2015.
Sufficient BRCA1 proteins in the brain protect against DNA damage, and physiological neuronal activation increases BRCA1 production.
Interesting research out of Nature Communications demonstrated that in the brains of Alzheimer’s patients, there is a reduction of the protective BRCA1 proteins. Amyloid-beta overexpression was shown to reduce BRCA1 in neuronal cultures. Further, increased stimulation of excitotoxic NDMA receptors was also shown to promote the proteasomal degradation of BRCA1.
The authors conclude that “BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.”
In functional medicine, we’re thinking about neuronal excitoxicity all of the time and how to protect against it. Many of us routinely measure quinolinic acid in our patients, understanding that it’s an inflammatory brain neurotoxin. QUIN specifically revs up the glutamatergic NMDA receptors, depletes local microglial cell glutathione and disrupts CNS neuronal plasticity. QUIN elevation has been implicated in neurodegenerative, neuropsychiatric and neurodevelopmental diseases including Alzheimer’s, Parkinson’s depression and autism. INF-gamma potently upregulates QUIN.
In QUINs role as potent NMDA agonist, it’s likely involved in depleting protective CNS BRCA1 levels, too.