Federico Sesti, a professor of neuroscience and cell biology at Rutgers’ Robert Wood Johnson Medical School, along with his research team, explored the balance between the ability cells' ability to detoxify the production of reactive oxygen species and cases where an imbalance leads to excessive oxidative stress. One of the key proteins that the researchers investigated is the voltage-gated potassium (K+) channel subfamily B member 1 (KCNB1), which accumulates and becomes toxic under conditions of stress, such as Alzheimer disease (AD) and traumatic brain injury (TBI).

The study revealed that patients with AD have much higher KCNB1 levels than individuals without the same neurologic condition, and in the cases of AD and TBI, this toxic accumulation is associated with damage that severely affects the mental status of the patient.   

The research team noted that previous researchers had established that free radicals were responsible for neurodegenerative disease, resulting in cellular dysfunction. They also noted that this is the first experimental evidence demonstrating that the changes resulting from predictable oxidative stress in the aging brain are exacerbated significantly in the presence of AD. Dasatinib (Sprycel), currently used in humans to treat leukemia, is now being tested in mice as a potential novel agent. Dasatinib is an oral multityrosine kinase inhibitor that inhibits tyrosine kinase, which acts as a signal transducer in several molecular pathways within the cell.

Researchers noted that this drug, and others like it, will soon lead the way to launching a clinical trial that will allow testing in humans. “The discovery of KCNB1’s oxidation/build-up was found through observation of both mouse and human brains, which is significant as most scientific studies do not usually go beyond observing animals,” said Sesti. “Further, KCBB1 channels may not only contribute to Alzheimer’s but also to other conditions of stress as it was found in a recent study that they are formed following brain trauma.”

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