Reactive Astroglia in the Ataxic Form of Creutzfeldt-Jakob Disease

Abstract

Transmissible spongiform encephalopathies (TSE) are sub-acute neurodegenerative disorders which include scrapie in sheep, bovine spongiform encephalopathy in cows, and Creutzfeldt-Jakob disease (CJD), kuru, Gerstmann-Straussler syndrome, and fatal familial insomnia in humans. The essential pathogenic component of TSE is an abnormal isoform of the prion protein designated PrPSc (for reviews and discussions see 1.) The naturally occurring, cellular prion protein, called PrPC, encoded by the Prnp gene, is expressed in neurons (2) and glia (3). PrPC is glycosilated and anchored to the plasma membrane, but little is known about its cellular function (see references in 1.) During the disease process, PrPC is converted into PrPSc in both neurons and astrocytes. The “converted” PrPSc is partly resistant to proteinase K digestion and has an altered conformational state whereby the amount α-helical structure decreases and the content of β-sheet increases (for review see 1). Prion-induced encephalopathies are characterized by intracerebral accumulation of PrPSc and deposition of PrP amyloid (for review see 1,4). The observation that Prnp knockout mice do not develop spontaneous scrapie (5) supports the view that the accumulation of PrPSc and PrP amyloid in the brain mediate neuronal toxicity in the central nervous system.