Microglia and prion disease: a review.

Prion diseases are characterized by the accumulation of PrPSc, an altered isoform of a normal cellular protein, PrPc. The prion hypothesis holds that the process of conformational change from PrPc to PrPSc under the influence of PrPSc constitutes the basic infectious mechanism in prion diseases. It is still unknown whether pathological changes in these diseases, which include spongiform degeneration, nerve cell loss and gliosis, are the result of neurotoxicity of PrPSc, loss of function of PrPc or some other mechanism. Recent in vitro findings using a synthetic peptide of human PrPc implicate microglia as a mediator of pathological changes. The mechanism of the toxicity of this peptide involves activation of microglia oxidative stress, and direct interactions with PrPc-synthesizing neurones that reduce their ability to cope with oxidative stress. Microglia thus seem to emerge as a mediator of neuronal degeneration and cell death in prion diseases.