title: Microglia and prion disease.
abstract: Gliosis is one of the hallmarks of the prion diseases. Prion diseases are fatal neurodegenerative conditions of low incidence made famous by both the hypothesis that a protein acts as the infectious agent without involvement of nucleic acid and the speculative idea that a disease of cattle, BSE, has spread to humans from the ingestion of prion-infected beef. Despite these unproved hypotheses, the aetiology of the prion diseases remains unsolved. The rapid degenerative course of the disease is preceded by a long incubation period with little or no symptoms. The rapid neurodegeneration in the disease follows from increased deposition of an abnormal isoform of a normal neuronal protein. Co-incident with the appearance of this abnormal protein is the activation of large numbers of microglia. Studies in cell culture with both the abnormal prion protein and a peptide-mimic suggest that neuronal degeneration occurs because of two concurrent effects. First, there is a reduction in neuronal resistance to toxic insults and, second, there is an increase in the production of toxic substances such as reactive oxygen species by microglia and a decrease in glutamate clearance by astrocytes. Microglia activated by the abnormal form of the prion protein also release cytokines, which stimulate changes in astrocytes such as proliferation. The implication of this is that microglia may play a major role in initiating the pathological changes in prion disease. This review discusses the role of microglia in these changes.
authors.affiliation: Department of Biochemistry, Cambridge University, Cambridge, CB2 1QW, United Kingdom. drb33@cam.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018620:PrPSc Proteins / Q000378:metabolism / Q000472:pathogenicity; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018620:PrPSc Proteins