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Harnessing the brain’s immune cells to stave off Alzheimer’s and other neurodegenerative diseases

Many neurodegenerative diseases, or conditions that result from the loss of function or death of brain cells, remain largely untreatable. Most available treatments target just one of the multiple processes that can lead to neurodegeneration, which may not be effective in completely addressing disease symptoms or progress, if at all.

But what if researchers harnessed the brain’s inherent capabilities to cleanse and heal itself? My colleagues and I in the Lukens Lab at the University of Virginia believe that the brain’s own immune system may hold the key to neurodegenerative disease treatment. In our research, we found a protein that could possibly be leveraged to help the brain’s immune cells, or microglia, stave off Alzheimer’s disease.

No available treatments for neurodegenerative diseases stop ongoing neurodegeneration while also helping affected areas in the body heal and recuperate.

In terms of failed treatments, Alzheimer’s disease is perhaps the most infamous of neurodegenerative diseases. Affecting more than 1 in 9 U.S. adults 65 and older, Alzheimer’s results from brain atrophy with the death of neurons and loss of the connections between them. These casualties contribute to memory and cognitive decline. Billions of dollars have been funneled into researching treatments for Alzheimer’s, but nearly every drug tested to date has failed in clinical trials.

Another common neurodegenerative disease in need of improved treatment options is multiple sclerosis. This autoimmune condition is caused by immune cells attacking the protective cover on neurons, known as myelin. Degrading myelin leads to communication difficulties between neurons and their connections with the rest of the body. Current treatments suppress the immune system and can have potentially debilitating side effects. Many of these treatment options fail to address the toxic effects of the myelin debris that accumulate in the nervous system, which can kill cells.

Microglia are immune cells masquerading as brain cells. In mice, microglia originate in the yolk sac of an embryo and then infiltrate the brain early in development. The origins and migration of microglia in people are still under study.

 

Microglia play important roles in healthy brain function. Like other immune cells, microglia respond rapidly to pathogens and damage. They help to clear injuries and mend afflicted tissue, and can also take an active role in fighting pathogens. Microglia can also regulate brain inflammation, a normal part of the immune response that can cause swelling and damage if left unchecked.

Microglia also support the health of other brain cells. For instance, they can release molecules that promote resilience, such as the protein BDNF, which is known to be beneficial for neuron survival and function.

But the keystone feature of microglia are their astounding janitorial skills. Of all brain cell types, microglia possess an exquisite ability to clean up gunk in the brain, including the damaged myelin in multiple sclerosis, pieces of dead cells and amyloid beta, a toxic protein that is a hallmark of Alzheimer’s. They accomplish this by consuming and breaking down debris in their environment, effectively eating up the garbage surrounding them and their neighboring cells.

Given the many essential roles microglia serve to maintain brain function, these cells may possess the capacity to address multiple arms of neurodegeneration-related dysfunction. Moreover, as lifelong residents of the brain, microglia are already educated in the best practices of brain protection. These factors put microglia in the perfect position for researchers to leverage their inherent abilities to protect against neurodegeneration.

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