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Mysteries of the microglia

Posted: 15th July 2020

The existence of the blood-brain barrier was long seen as proof of the brain being off limits to the immune system. 
The dense constellation of cells that form the barrier was thought to limit access to the brain, and like a bouncer at an exclusive nightclub, rebuff entry by the immune system’s white blood cells. 
However, recent evidence suggests that the brain has its own built-in immune system, with the white blood cell’s cousins, the microglia, already in the club. 
These microglia are increasingly seen as the new frontier in tackling neuro-degenerative diseases like Alzheimer’s and multiple sclerosis. 
Multiple sclerosis is an autoimmune condition in which the immune system progressively eats away at the protective covering of nerves, resulting in damage that disrupts communication between the brain and the body. More than 25,000 Australians are affected.
Dr Jon Gooi says that many questions regarding the disease are yet to be answered. And it is hoped that microglia may hold the key. 
“Microglia act as the first and main form of active immune defence in the brain,” says Jon. 
He explains that microglia are very busy cells, constantly on patrol for signs of trouble. If they detect a threat, like an invading pathogen or a damaged nerve cell, they kick into action and literally gobble it up. 
But it seems they may also have a dark side. In some disease states, like multiple sclerosis, it is thought that the cells become overactive, triggering inflammation in the brain and contributing to the disease.
“If we could understand how the microglia are controlled, we might be able to better understand certain neurodegenerative diseases. And figuring out how to manipulate these cells might provide solutions for diseases like multiple sclerosis.”
Jon and the team are designing drugs that can interact with a receptor found on the surface of microglia that is thought to modify the behaviour of the cells. They hope that these drugs may be able to reduce the inflammation caused by microglia.
Using sophisticated computer-based modelling methods, the researchers have sifted through 5 million compounds and identified 12 promising drug candidates that look like they might interact with the receptor. They will test the effect of these candidates on microglia grown in the laboratory.
“The tools that we develop will help us to dissect the exact role of microglia in the disease process – whether they help or hinder – and may also provide new drug candidates for the treatment of multiple sclerosis.”

For more information please see: Structural biology