Researchers have discovered a new mechanism that may contribute to Alzheimer’s disease and traumatic brain injury. They now hope to launch a clinical trial to test a potential treatment in humans.
What causes Alzheimer’s disease is unknown, but a popular theory suggests a protein known as amyloid-beta slowly builds up a plaque in the brains of people with the disease. But in a recent study in the journal Cell Death & Disease, researchers looked at a new mechanism, which involves a non-amyloid-beta protein, a potassium channel referred to as KCNB1.
Under conditions of stress in a brain Alzheimer’s disease affects, KCNB1 builds up and becomes toxic to neurons and then promotes the production of amyloid-beta. A chemical process commonly known as oxidation causes the build-up of KCNB1 channels.
KCNB1 builds up and becomes toxic to neurons and then promotes the production of amyloid-beta.
“Indeed, scientists have known for a long time that during aging or in neurodegenerative disease cells produce free radicals,” says study coauthor Federico Sesti, a professor of neuroscience and cell biology at Rutgers University’s Robert Wood Johnson Medical School. “Free radicals are toxic molecules that can cause a reaction that results in lost electrons in important cellular components, including the channels.”
The study finds that in brains with Alzheimer’s disease, the build-up of KCNB1 was much higher compared to normal brains.
“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,” says 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.”
In the cases of Alzheimer’s and traumatic brain injury, the build-up of KCNB1 is associated with severe damage of mental function. As a result of this discovery, Sesti successfully tested a drug called Sprycel in mice. The drug is used to treat patients with leukemia.
“Our study shows that this drug and similar ones could potentially be used to treat Alzheimer’s, a discovery that leads the way to launching a clinical trial to test this drug in humans,” Sesti says.
Source: Rutgers University