Microglial cells respond to amyloidogenic PrP peptide by the production ofinflammatory cytokines

THE scrapie isoform of the prion protein (PrPres) induces neurodegeneration and gliosis in the central nervous system. These features may be reproduce d in vitro on exposure of neuronal and glial cultures to PrPres and the pep tide HuPr P106-126. In the present study, me investigated the role of micro glial cells and astrocytes in the pathological process by studying their mo lecular response to PrP 106-126 exposure. PrP 106-126 elicited a specific o verproduction of pro-inflammatory cytokines IL1 beta and IL6 in microglial cells (but not increased expression of TNF alpha, IL10, and TGF beta 1) and over-expression of GFAP in astrocytes. These effects were strictly depende nt on the ability of the peptide to form amyloid fibrils, These data strong ly suggest that microglial cells contribute to prion-related neurodegenerat ive processes by producing proinflammatory cytokines in the brain areas of amyloid PrP deposition. NeuroReport 10:723-729 (C) 1999 Lippincott Williams & Wilkins.