Researchers at UVA Health have identified a brain molecule that coordinates the immune system’s reactions to multiple sclerosis (MS) and Alzheimer’s disease, potentially enabling medical professionals to boost the body’s power to combat these and other deadly neurological conditions.
The researchers discovered a protein called a kinase that is essential for both clearing plaque buildup linked with Alzheimer’s disease and preventing the debris buildup that causes MS.
The researchers demonstrated that it accomplishes this by guiding the activity of brain cleaners known as microglia. These immune cells were previously completely overlooked by scientists, but have recently proven to be critical participants in brain health.
The researchers report that UVA’s significant new results may one day allow physicians to increase microglia activation to treat or protect people with Alzheimer’s, MS, and other neurodegenerative disorders.
“Unfortunately, medical doctors do not currently possess effective treatments to target the root causes of most neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or ALS [amyotrophic lateral sclerosis, commonly called Lou Gehrig’s disease],” points out senior researcher John Lukens.
“In our studies,” add the researcher, “we have discovered a master controller of the cell type and processes that are required to protect the brain from these disorders.”
Their paper “further shows that targeting this novel pathway provides a potent strategy to eliminate the toxic culprits that cause memory loss and impaired motor control in neurodegenerative disease.”
Many neurodegenerative disorders, including Alzheimer’s and Multiple Sclerosis, are believed to result from the brain’s inability to eliminate toxic buildup.
Recent developments in neuroscience research have highlighted the role of microglia in removing harmful debris from the brain, but UVA’s latest discovery provides practical insights into how this cleaning process occurs – and the disastrous repercussions when it does not.
Using a mouse model of Alzheimer’s disease, they found that a lack of the molecule they called “spleen tyrosine kinase” caused plaque to build up in the brains of the mice, which led to memory loss similar to what people with Alzheimer’s experience.
Also, by activating this molecule and microglia in the brain, the neuroscientists were able to reduce the buildup of plaque. This suggests a possible way to treat human patients, but that would take a lot more research and testing.
“Our work has described a critical element of microglial function during Alzheimer’s disease and MS,” explains first author Hannah Ennerfelt. “Understanding the underlying biology of these cells during neurodegeneration may allow for scientists and doctors to develop increasingly informed and effective therapeutic interventions.”
In the meantime, a lack of the molecule in a mouse model of MS resulted in the accumulation of damaged myelin, a protective coating on nerve cells. When myelin is destroyed, cells are unable to correctly transfer messages, resulting in MS symptoms such as movement issues and muscle spasms.
In a new scientific paper, the UVA researchers say that the molecule they found, called SYK, is “critically involved” in the important removal of myelin debris.
A key participant in the investigation, Elizabeth L. Frost, PhD, stated that, “If boosting SYK activity in microglia can decrease the amount of myelin debris in MS lesions, developing new drugs to target SYK could stop the progression of MS and help to reverse the damage.”
Given that the majority of the MS treatments that are currently on the market suppress adaptive immunity, this is a very interesting alternative. These immunosuppressive medications increase the risk of potentially deadly side effects such progressive multifocal leukoencephalopathy and infection susceptibility. Additionally, there are currently very few therapy options available for MS individuals whose disease does not strongly involve the immune system.
“Targeting SYK in microglia,” she adds, “would circumvent multiple limitations of present-day therapeutics for MS.”
The researchers believe that targeting the molecule to increase the immune activity in the brain may provide a strategy to treat not only Alzheimer’s and MS but a “spectrum” of neurodegenerative illnesses in light of their encouraging findings.
“These findings are especially exciting because they point to a treatment avenue in which we could alter the behavior of these native brain cells, microglia, to behave in a more neuroprotective way,” adds researcher Coco Holliday, a UVA undergraduate working in the Lukens lab. “It could potentially be applied to a variety of different neurological diseases that all share the problem of a buildup of toxic waste in the brain. It’s been a very exciting project to be a part of.”
Image Credit: Dan Addison | University of Virginia Communications
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