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Understanding glial cells to help fight neurodegenerative diseases
Publication date: 12/03/18
Brain Awareness Week was held in the first week of March, giving attendees an opportunity to investigate one of its little-known components: glial cells. We met with Frank Pfrieger, a researcher at the Institute of Cellular and Integrative Neurosciences (INCI), which seeks to unravel the mystery of these cells and their impact on the development of certain neurodegenerative diseases.
In his laboratory, Frank Pfrieger, director of research at the CNRS (National Centre for Scientific Research), is interested in the interactions between neurons and glial cells. More specifically, since 2001, he has been exploring the link between astrocytes (see box) and cholesterol, which is crucial in order for the brain to function properly. Understanding this link is essential in order to treat certain neurodegenerative diseases such as Niemann-Pick Type C, which can lead to the death of sufferers before the age of 10 in its most severe form.
"During our work, we tried to find out what synthesises cholesterol in the brain. One of the hypotheses is that astrocytes make cholesterol for the neurons and deliver it. With this in mind, we came across Niemann-Pick Disease." This genetic neurodegenerative disease is the result of a mutation in one of the two proteins responsible for the redistribution of cholesterol within cells. When they fail, cholesterol builds up. "The question is why this build-up leads to the death of certain neurons and the specific neurological symptoms encountered", says Frank Pfrieger.
A treatment under review
The other question concerns the role that astrocytes play in degeneration: "Do they cause neurons to die or do they actually allow them to live longer?" asks the researcher, who points out that astrocytes can exist in two forms: one is positive for the lifespan of neurons, while the other is negative. "For the time being, we don't know if these two forms are simultaneous or if they exist one after the other.”
In terms of his methods, the researcher works on cell cultures but also on genetically modified mice, allowing him to manipulate astrocytes in vivo. Frank Pfrieger created two strains of mice in 2007, and these are now used in laboratories around the world.
More recently, a treatment based on cyclodextrin (currently undergoing clinical trials) has been devised to delay cell degeneration in the case of Niemann-Pick Disease. "We observed that this substance allows neurons to expel cholesterol, which is then consumed by the glia. The glia therefore help to clean things up," said Frank Pfrieger, whose discovery is due to be published soon.