Most individuals diagnosed with Alzheimer’s disease (AD), the most common type of dementia, are 65 or older. This makes age one of the most prominent risk factors for this devastating disease. As medical researchers worldwide race for a cure, a recent study from the University of Virginia School of Medicine could point the way forward. The study may explain why aging is associated with increased AD risk, while also presenting a potentially druggable target within the human immune system. Read on for more information about the research, which was published May 23 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Could This Immune System Molecule Help Cure AD?
Researchers have long sought effective targets for AD treatment. The University of Virginia team revealed a strong new contender: a molecule within the immune system known as stimulator of interferon genes, or STING. According to the published research, the team initially aimed to investigate how discrete innate immune signaling pathways contribute to the progression of AD using genetic targeting methods. Their findings led them to STING, a major innate immune adaptor molecule that helps clear viruses and stressed cells harboring DNA damage from the brain.
The researchers wrote that STING is best known for “orchestrating immune signaling in response to both pathogen- and host-derived DNA,” an important role in the brain’s immune system. However, overactive STING may have a downside.
Overriding Detrimental Neurological Immune Responses
While STING plays an important role in immune function, it can become hyperactive. This can occur in a number of ways. For example, mutations in the gene encoding STING can cause hyperactivity. STING also responds to the presence of pathogens, which can lead to overactive immune responses, including inflammation and tissue damage. In addition, STING may overreact to the naturally occurring DNA damage that accompanies aging. The University of Virginia team wanted to explore this hyperactivity.
To do so, the researchers worked with 5xFAD mice, a widely used transgenic mouse model for studying AD. Blocking the STING molecule’s activity in mice ultimately helped prevent AD plaque formation. It also notably altered microglial activity, potentially protecting the 5xFAD mice from mental decline associated with neurodegeneration, the researchers say.
STING Provides Promising Treatment Target
Experts have struggled to identify an effective target for developing new AD treatments. Other potentially druggable molecules present treatment barriers; for example, they may be targeted only at very specific stages in AD progression. Blocking STING, however, seems to stop the disease in its tracks by treating a potential root cause of cognitive decline.
“We found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage and improved memory function in Alzheimer’s model mice,” said researcher Jessica Thanos in a press release. “Together, these findings suggest that STING drives detrimental immune responses in the brain that exacerbate neuronal damage and contribute to cognitive decline in Alzheimer’s disease.”
In other words, AD could be partly caused by misguided immune system actions as we age. “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 researcher John Lukens in the release.
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Developing treatments to control overactive STING could have a domino effect, potentially helping to treat conditions like Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and other types of dementia. Further research into this molecule could have massive benefits.
Scantox Neuro offers in vivo research with 5xFAD mice and related behavioral, biochemical, and histological analysis methods. Furthermore, several in vitro models to study AD are available and can be adjusted to fit your needs.
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