Understanding the natural process that limits the effects of neurodegenerative diseases could help develop therapies. According to a study by researchers at the Roslin Institute, an immune cell in the brain plays a role in limiting the damage that occurs in neurodegenerative diseases.Known as microglia, these cells protect neurons from damage caused by prion disease, which occurs when prion proteins fold incorrectly in the brain.[scald=47503:sdl_editor_representation {"alt":"Professor Neil Mabbott","caption":"Professor Neil Mabbott"}]The results of the study, led by a Roslin Institute team, could influence the development of drugs to treat prion disease and other neurodegenerative diseases such as Alzheimer's and Parkinson's.Limit damageThe researchers studied how microglia affect prion disease.Their study followed up on previous research that had shown that the disease progresses faster and there is increased accumulation of prions in the brain when microglia levels are reduced.This suggests that microglia play a role in destroying prions in the brain and mitigating the effects of the disease.The new study, conducted in mice, shows instead that microglia protect the brain not by eliminating prions but by limiting the activity of brain cells of a different type, called astrocytes, which produce toxins in response to damage.In mice lacking microglia, the damaging activity of astrocytes was greater, their neurotoxic response was much stronger, and the mice developed prion disease much faster.The rate of prion accumulation in the brain was no different, but disease progression was faster than in mice with microglia.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 Mabbott, Roslin InstituteThese results suggest that the role of microglia in limiting disease effects is not to destroy prions, but rather to limit the neurotoxic activity of astrocytes.The study, published in the journal Glia, was conducted in collaboration with colleagues at the University of Queensland and the University of Edinburgh's Centre for Discovery Brain Sciences and Queen's Medical Research Institute.Related LinksThe Roslin InstituteMicroglia deficiency accelerates prion disease but does not enhance prion accumulation in the brainProf Neil Mabbott profile Publication date 03 Nov, 2022
