Summary: Microglia are the brain’s immune cells. A new study shows that when they meet debris, they make a protein called SYK, and SYK drives their cleanup work. Boosting SYK could change the course of neurodegenerative disorders, the diseases where brain cells slowly die. Researchers have started to look at how a faulty brain immune system plays a part in these disorders, with a focus on microglia. These diseases are on the rise, and there is no good treatment for them. So conditions like Alzheimer’s and multiple sclerosis have become a major public health concern.
The rise in neurodegenerative disorders has truly surprised researchers. Studies show they now affect one in nine adults in the US older than 65 years of age. Disorders like Alzheimer’s have also become a major cause of death and disability.
Yet even as these brain disorders rise, 100 years of research has failed to explain much about them. Many studies could not explain what exactly causes brain disorders or how they develop. So it is no surprise that there are no reliable markers (biomarkers) and treatments for brain disorders like Alzheimer’s or multiple sclerosis.
This big failure to understand and treat brain disorders like Alzheimer’s has forced researchers to rethink their approach. Most researchers now say the failure may come from focusing too much on neurons (nerve cells).
In these disorders, neurons start dying for many reasons. So researchers have looked for ways to slow or stop that. But they often forgot that the brain has many other types of cells.
Glial cells outnumber neurons in the brain and play many roles. They support the neurons and might even modulate their working by influencing neuronal synapses. More importantly, glial cells form the brain’s immune system. Hence, they are vital to the brain’s capacity to defend, protect, and cleanse. Thus, researchers now think it is time to focus on glial cells like microglia.
Can the brain’s immune cells help treat Alzheimer’s disease?
Microglia are abundant in the brain. They primarily act as immune cells. Thus, there is a firm reason to believe they may help prevent neurodegenerative disorders. However, there are specific challenges in tweaking these cells. Brain immunity is still poorly understood by science. Science is still unsure of how these cells form in the brain during early development stages. After all, microglial cells do not share many traits with other immune cells circulating in the blood.
Microglial cells play many roles in the brain. They protect brain cells from irritants and foreign material. They also keep brain cells healthy. They control the brain’s inflammation, clear debris, reduce swelling and release chemicals that make the brain more resilient. They also make molecules like BDNF that help neurons survive.
But researchers say one of the most important jobs of microglia is clearing debris. They act as the brain’s janitors. This matters because many brain diseases like Alzheimer’s come from a buildup of faulty proteins like beta-amyloid. So if science can learn to steer microglia, it would be a more natural and safer way to clear faulty proteins and protect the brain.
The new study set out to do just that. First, researchers looked at proteins that can change how microglia behave. Then they zeroed in on a protein called SYK. They noticed that when microglia meet debris, they make more of this protein.
In the study, researchers blocked SYK in microglia in mice with an Alzheimer’s-like disease. Amyloid protein suddenly built up faster. In mice with a multiple sclerosis-like disease, turning down SYK let more myelin debris pile up, and the disease got worse.
Blocking SYK worsened Alzheimer’s and multiple sclerosis symptoms in these mice. This indicates that SYK plays a key role in controlling microglia and fighting brain-cell loss.
The researchers also found how SYK helps. The protein moves toward the debris and signals microglia to clear or destroy it. So it tells microglia to clean up and remove toxins. That helps prevent neuron death and helps neurons regrow. Researchers say boosting SYK could create super microglia that might even help reverse these brain diseases.
Frequently asked questions
What are microglia?
Microglia are the brain’s own immune cells, a type of glial cell. They protect brain cells from irritants and foreign material, calm inflammation, reduce swelling, clear away debris and release chemicals that make the brain more resilient. They also make molecules such as BDNF that help neurons survive. They share few traits with the immune cells that circulate in the blood.
What clears amyloid plaque from the brain?
Microglia do much of that work. They act as the brain’s janitors, and removing debris is one of their most important jobs. That matters because Alzheimer’s disease is driven by a buildup of faulty proteins such as beta-amyloid. If science can learn to steer microglia, it would be a more natural and safer way to clear those proteins and protect neurons.
What is SYK, and what does it have to do with Alzheimer’s?
SYK is a protein that microglia make more of when they run into debris. It moves toward the debris and signals the microglia to clean it up. In mice with Alzheimer’s, blocking SYK caused amyloid to pile up faster and symptoms to worsen. In mice with multiple sclerosis, it left more myelin debris behind. These were animal studies, not human trials.
How common are neurodegenerative diseases like Alzheimer’s?
They now affect one in nine adults in the U.S. older than 65, and the rise has surprised researchers. Alzheimer’s has become a major cause of disability and death. Yet there are still no reliable markers and no good treatment for disorders like Alzheimer’s or multiple sclerosis. That is why they have become a major public health concern.
Why has Alzheimer’s research failed to find a cure?
A hundred years of research has not explained the exact cause of these disorders. Most researchers now think the field focused too narrowly on neurons, trying to slow their death while overlooking the other cells in the brain. Glial cells outnumber neurons, support them and form the brain’s immune system. That is why attention has shifted to microglia.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
