Upregulation of the Genes Encoding Lysosomal Hydrolases, a Perforin-Like Protein, and Peroxidases in the Brains of Mice Affected with an Experimental Prion Disease

• DOI: 10.1128/jvi.74.1.411-417.2000
• Publication Date: 2009-04-23T21:08:16Z
• Authors: Juraj Kopacek; Suehiro Sakaguchi; Kazuto Shigematsu; Noriyuki Nishida; Ryuichirou Atarashi; Ryota Nakaoke; Ryozo Moriuchi; Masami Niwa; Shigeru Katamine
• Keywords: Peroxiredoxin

ABSTRACT In an attempt to identify the molecules involved in pathogenesis of prion diseases, we performed cDNA subtraction on brain tissues mice affected with experimental disease and unaffected control. The genes identified as being upregulated prion-affected tissue included those encoding a series lysosomal hydrolases (lysozyme M both isoforms β- N -acetylhexosaminidase), perforin-like protein (macrophage proliferation-specific gene-1 [MPS-1]), oxygen radical scavenger (peroxiredoxin). Dramatic increases expression level occurred at between 12 16 weeks after intracerebral inoculation prion, coinciding onset spongiform degeneration. proteinase K-resistant (PrP Sc ) became detectable by immunoblotting well before weeks, suggesting causal relationship this gene activation. Immunohistochemistry paired situ hybridization sections revealed that peroxiredoxin was only astrocytes noted throughout tissue. On other hand, for MPS-1 were overexpressed exclusively microglia, which colocalized morphological changes. A crucial role microglia degeneration their production neurotoxic substances, possibly via aberrant activation system, would have be considered.