New data in both animal models and human patients points to a previously underappreciated role microglia also play in the development of neurodegenerative disease. Many genetic risk factors for diseases like Alzheimer’s and multiple sclerosis are strongly linked to abnormal microglia function. These findings support an accumulating number of animal studies suggesting that disruptions to microglial function may contribute to neurologic disease onset and severity.

This raises the next logical question: How can researchers harness microglia to protect the nervous system against neurodegeneration?

In our lab’s recent study, we keyed in on a crucial protein called SYK that microglia use to manipulate their response to neurodegeneration.

Our collaborators found that microglia dial up the activity of SYK when they encounter debris in their environment, such as amyloid beta in Alzheimer’s or myelin debris in multiple sclerosis. When we inhibited SYK function in microglia, we found that twice as much amyloid beta accumulated in Alzheimer’s mouse models and six times as much myelin debris in multiple sclerosis mouse models.

Blocking SYK function in the microglia of Alzheimer’s mouse models also worsened neuronal health, indicated by increasing levels of toxic neuronal proteins and a surge in the number of dying neurons. This correlated with hastened cognitive decline, as the mice failed to learn a spatial memory test. Similarly, impairing SYK in multiple sclerosis mouse models exacerbated motor dysfunction and hindered myelin repair. These findings indicate that microglia use SYK to protect the brain from neurodegeneration.

But how does SYK protect the nervous system against damage and degeneration? We found that microglia use SYK to migrate toward debris in the brain. It also helps microglia remove and destroy this debris by stimulating other proteins involved in cleanup processes. These jobs support the idea that SYK helps microglia protect the brain by charging them to remove toxic materials.

Finally, we wanted to figure out if we could leverage SYK to create “super microglia” that could help clean up debris before it makes neurodegeneration worse. When we gave mice a drug that boosted SYK function, we found that Alzheimer’s mouse models had lower levels of plaque accumulation in their brains one week after receiving the drug. This finding points to the potential of increasing microglia activity to treat Alzheimer’s disease.

Future studies will be necessary to see whether creating a super microglia cleanup crew to treat neurodegenerative diseases is beneficial in people. But our results suggest that microglia already play a key role in preventing neurodegenerative diseases by helping to remove toxic waste in the nervous system and promoting the healing of damaged areas.

It’s possible to have too much of a good thing, though. Excessive inflammation driven by microglia could make neurologic disease worse. We believe that equipping microglia with the proper instructions to carry out their beneficial functions without causing further damage could one day help treat and prevent neurodegenerative disease.

This article is republished from The Conversation, an independent nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Kristine Zengeler, University of Virginia. Like this article? subscribe to our weekly newsletter.

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This work was supported by funding from the NIH (1RF1AG071996-01, R01NS106383), The Alzheimer’s Association (ADSF-21-816651), the Cure Alzheimer’s Fund, The Owens Family Foundation, and a Wagner Scholarship