Microglia and the pathogenesis of spongiform encephalopathies

Alterations in the phenotype and function of microglia, the resident mononu clear phagocytes of the central nervous system, are among the earliest indi cations of pathology within the brain and spinal cord. The prion diseases, also known as spongiform encephalopathies, are fatal neurodegenerative diso rders with sporadic, genetic or acquired infectious manifestations. A hallm ark of all prion diseases is the aberrant metabolism and resulting accumula tion of the prion protein. Conversion of the normal cellular protein [PrPc] into the abnormal pathogenic (or disease-causing) isoform [PrPSc] involves a conformational alteration whereby the alpha -helical content is transfor med into beta -sheet. The histological characteristics of these disorders a re spongiform change, astrocytosis, neuronal loss and progressive accumulat ion of the protease-resistant prion isoform. An additional upregulation in microglial response has been reported in Kuru, Creutzfeldt-Jakob disease (C JD), Gerstmann-Straussler-Scheinker syndrome (GSS), scrapie, in transgenic murine models and in culture, where microglial activation often accompanies prion protein deposition and neuronal loss. This article will review the r oles of microglia in spongiform encephalopathies. (C) 2001 Elsevier Science B.V. All rights reserved.