Memory loss, changes in communication, and confusion are all signs and symptoms of neurodegenerative conditions like dementia. But what is going on inside the brain?
A new study finds that cell stress could be to blame. Turning off this stress response rescues brain cells like those affected by early-onset dementia, offering a promising new way to combat degenerative brain diseases.
As the U.S. population ages, the prevalence of neurodegenerative conditions, including Alzheimer’s and Parkinson’s, increases. But some degenerative brain diseases start early in life; early-onset dementia, for example, occurs when people develop dementia symptoms before the age of 65.
Current Treatments Focus on Protein Buildup in the Brain
It is well-known that neurodegenerative diseases like Alzheimer’s are characterized by an abnormal buildup of two key proteins, amyloid and tau, in the brain. These clumps, called aggregates, are believed to cause the brain cells to function less well—as seen with memory loss—and to ultimately die.As a result, treatments focus on dissolving and eliminating the accumulated aggregates.
However, the team of scientists at the University of California–Berkeley (UC Berkeley) conducting the new study found that some of these degenerative conditions are driven by brain cell stress response rather than the protein aggregates themselves.
“We realized that even though there was this correlation, there was no clear causative link between a protein aggregate and the neuronal deaths,” lead researcher Michael Rapé, professor and head of the Division of Molecular Therapeutics at UC Berkeley, told The Epoch Times.
Nonstop Stress Response Kills Brain Cells
How does your brain keep cognition sharp?Mr. Rapé has a simple analogy to explain this mechanism: You not only need to clean up your room but also turn out the light before going to bed. If you don’t turn off the light, you can’t fall asleep.
The machine that cleans up the debris in the brain and “silences” the stress response is called the silencing factor of the integrated stress response (SIFI).
But, when SIFI can’t do its job, the proteins continue to accumulate, triggering a nonstop stress response. In people whose stress response stays activated—as if the lights were left on night after night—the cells die.
“The SIFI complex is needed for cells to survive when they are stressed out by proteins not being delivered into the mitochondria,” explained Mr. Rapé. “If they don’t get to the mitochondria, [instead] the proteins form aggregates” in and around the brain cells.
Mitochondria are often called the powerhouse of cells, breaking down food into usable energy for cells. When the proteins are diverted from the mitochondria, it triggers a stress response to clear out the mess.
Silencing Stress Saves Cells
The team administered a drug compound that successfully turned off the stress response and, in turn, rescued cells that mimic those affected by early-onset dementia. This result opens the door to potential new ways to treat neurodegenerative diseases.The team also found that the therapeutic drugs worked without dissolving the protein clumps. This finding suggests that the real danger from these aggregates is how they perpetuate cellular stress.
“You don’t have to worry about completely getting rid of large aggregates, which changes how we think about treating neurodegenerative diseases,” added Mr. Rapé.
Based on the research, Mr. Rapé believes the “best way to treat neurodegenerative disease would be a combination therapy that keeps aggregates at bay and silences stress response signaling at the same time.”
