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Brain immune cell limits impact of degenerative disease

Understanding the natural process that limits the impact of neurodegenerative conditions could help develop therapies.

An immune cell found in the brain has a role in limiting the damage caused during neurodegenerative disorders, a study suggests.

These cells, known as microglia, protect nerve cells from damage caused by prion disease, which occurs when prion proteins in the brain fold incorrectly, research has found.

Insights from the study, led by a Roslin Institute team, could inform development of drugs to treat prion diseases and other neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.

Limiting damage

Researchers sought to investigate how microglia affected prion disease.

Their study followed previous research indicating that when microglia levels were reduced, disease progressed faster and there was an increased accumulation of prions in the brain.

This suggested that microglia had a role in destroying prions in the brain and lessening the impact of disease.

The new study, carried out in mice, instead shows that microglia protect the brain not by removing prions, but by limiting activity in brain cells of another type, known as astrocytes, which produce toxins in response to damage.

In mice without microglia, there was more harmful activity in astrocytes, their neurotoxic response was much stronger and mice developed prion disease much quicker.

The rate of prion accumulation in the brain was no different, but the progress of disease was faster, compared with mice that had microglia.

These results suggest that microglia’s role in limiting the impact of disease did not involve the destruction of prions, but rather to limit the neurotoxic activity of astrocytes.

The study, published in the journal Glia, was carried out with colleagues at the University of Queensland and the University of Edinburgh’s Centre for Discovery Brain Sciences and Queen’s Medical Research Institute.

Our results reveal a novel way in which the microglia help to protect the brain from prion disease. There are no therapies available to treat prion diseases. If we can identify the biological mechanisms by which immune cells in the brain can prevent other cells such as astrocytes from releasing toxins in response to disease, we may be able to design new therapies to treat prion diseases and other important neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.

Professor Neil MabbottRoslin Institute

** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **

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