Theoretical analysis of the implication of PrP in neuronal death during transmissible subacute spongiform encephalopathies: hypothesis of a PrP oligomeric channel.

Transmissible subacute spongiform encephalopathies (TSE) are animal and human neurodegenerative diseases. The nature of the transmissible agent remains unknown. The specific molecular marker of these diseases is the abnormal isoform of the prion protein (PrP).

Enhanced levels of scrapie responsive gene mRNA in BSE-infected mouse brain.

The expression of the mRNA of nine scrapie responsive genes was analyzed in the brains of FVB/N mice infected with bovine spongiform encephalopathy (BSE). The RNA transcripts of eight genes were overexpressed to a comparable extent in both BSE-infected and scrapie-infected mice, indicating a common series of pathogenic events in the two transmissible spongiform encephalopathies (TSEs). In contrast, the serine proteinase inhibitor spi 2, an analogue of the human alpha-1 antichymotrypsin gene, was overexpressed to a greater extent in the brains of scrapie-infected animals than in animals infected with BSE, reflecting either an agent specific or a mouse strain specific response.

Search for a nuclear localization signal in the prion protein.

Spongiform transmissible encephalopathies are neurodegenerative diseases characterized by the accumulation, in infected brains, of a pathological form of a normal host-encoded protein called PrP. Previous data have shown that PrP could interact with cytosolic factors, including nuclear molecules, emphasizing the possible function of such interactions. Moreover, in infected cells, PrP is observed not only at the plasma membrane but also in the nuclear compartment.

Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein.

The agent responsible for transmissible spongiform encephalopathies (TSEs) is thought to be a malfolded, protease-resistant version (PrPres) of the normal cellular prion protein (PrP). The interspecies transmission of bovine spongiform encephalopathy (BSE) to mice was studied. Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres.