November 21, 2017
Scientists have known for a long time that the accumulation of two proteins, beta-amyloid and tau, signify Alzheimer’s presence in the brain. But now, they’re seeing that the accumulation of tau goes hand in hand with another brain change: the formation of what researchers are calling ‘stress granules.’ Using this information, researchers at Boston University have found a potential new way to approach Alzheimer’s treatment.
Stress granules are tiny bundles of RNA protein that appear in cells that have been exposed to factors like heat, starvation, temperature change, viruses and toxins. They show up when there’s a need for the brain to produce protective proteins. Much like a person, a cell can start to shut down when it’s stressed, and it rounds up the RNA that usually carry out the processes of the cell. Those are the stress granules that are stored in the cell for safekeeping. When the stressful event passes, the RNA is released—or at least it’s supposed to be.
In diseases like Alzheimer’s, the stress granules accumulate, driving the production of tau, which leads to death of brain cells seen in dementia. In an animal study, the Boston University scientists reduced the protein T1A1, which is required for stress granule formation. Doing so improved nerve cell health, reduced the type and amount of tau clumping and improved memory and life expectancy.
What was most interesting, is that reducing the stress granules produced more tau—but it was a different kind of tau, and it did not have the same toxic effect on the brain as tau typical of Alzheimer’s.
According to study author Benjamin Wolozin, M.D., Ph.D., professor of pharmacology & experimental therapeutics at Boston University School of Medicine, the types of events that can trigger stress granules include the accumulation of beta-amyloid, cardiovascular disease that weakens blood and oxygen flow to the brain, and even stressful periods in life. “I have a colleague that has found the surprising result that severe stress, [like the kind that accompanies depression], can trigger stress granules,” said Wolozin.
While mouse models do not always translate to the same results in human brains, the team is hopeful that this experiment will point to new approaches to treating dementia, according to Wolozin.
The study appeared in the journal Nature Neuroscience. Wolozin’s work is funded by organizations like the National Institutes of Health, the Alzheimer’s Association and the Cure Alzheimer’s Fund. He also has a biotechnology company that aims to develop medicines to reduce stress granules in diseases like Alzheimer’s.