Our John Lukens, PhD, and his team have identified a promising target to develop new treatments for Alzheimer's, Parkinson's and other memory-stealing conditions.
The team's latest research reveals that a particular molecule produced by our immune systems drives the formation of both amyloid plaques and tau protein tangles in the brain-- the two leading suspects thought to cause Alzheimer's.
Notably, blocking the molecule, called STING, prevented cognitive decline in lab mice.
“Our findings demonstrate that the DNA damage that naturally accumulates during aging triggers STING-mediated brain inflammation and neuronal damage in Alzheimer’s disease,” said Professor Lukens, director of our Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases. “These results help to explain why aging is associated with increased Alzheimer’s risk and uncover a novel pathway to target in the treatment of neurodegenerative diseases.”
The new findings may make STING sound like a villain on first blush, but it's more complicated than that. STING is actually an important defender of the brain, directing the removal of viruses and stressed cells with DNA damage. But STING can also become hyperactive. When this happens, it causes harmful inflammation and tissue damage. The researchers believe that its efforts to repair the brain may instead be driving Alzheimer's and other neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), dementia and other memory-robbing conditions.
That suggests that finding ways to control its activity -- limiting its harmful effects while preserving the beneficial ones -- could have big benefits for many neurodegenerative conditions.
“We are only beginning to understand the complex role of innate immune activation in the brain, and this is especially true in both normal and pathological aging,” researcher Jessica Thanos said. “If we can pinpoint which cells and signals sustain that activation, we will be in a much better position to intervene effectively in disease.”
Further, STING appears to play a key role throughout the development of Alzheimer's, whereas other molecules scientists have looked at lack that robust involvement. Those molecules also could be targeted only at very specific – and very limited – stages in the disease’s progression, whereas the window for targeting STING could be far broader.