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Effect of Congo Red on Wild‐Type and Mutated Prion Proteins in Cultured Cells
Author(s) -
Milhavet Olliver,
Mangé Alain,
Casanova Danielle,
Lehmann Sylvain
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740222.x
Subject(s) - scrapie , gene isoform , prion protein , in vitro , congo red , transfection , in vivo , biology , protease , wild type , mutant , chemistry , microbiology and biotechnology , biochemistry , gene , genetics , enzyme , medicine , disease , organic chemistry , pathology , adsorption
Transmissible spongiform encephalopathies form a group of fatal neurodegenerative disorders that have the unique property of being infectious, sporadic, or genetic in origin. Although some doubts remain on the nature of the responsible agent of these diseases, it is clear that a protein called PrP Sc (which stands for the scrapie isoform of the prion protein) has a central role in their pathology. PrP Sc represents a conformational variant of a normal protein of the host: the cellular isoform of the prion protein, or PrP C . Compounds such as glycosaminoglycans and Congo red (CR) have been shown to interfere with both in vitro and in vivo PrP Sc formation. It was hypothesized that CR acts by overstabilizing the conformation of PrP Sc molecules or by modifying trafficking of PrP C . Using transfected cells expressing 3F4‐tagged mouse PrPs, we show here that CR does not interfere with conversion of PrP molecules carrying pathogenic mutations. On the contrary, after incubation with the drug, some of their properties, such as insolubility and protease resistance, are enhanced and are even acquired by the wild‐type molecule. This last observation suggests an alternative mechanism of action of CR and leads us to reconsider the relationship between the biochemical properties of PrP and conformational alteration of the protein.