Abstract
Transmissible spongiform encephalopathies (TSEs) are a family of invariably fatal neurodegenerative diseases. This group includes scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are characterized by the accumulation of the abnormal isoform prion protein (PrPSc), which is a misfolded version of the cellular prion protein (PrPC) and is resistant to enzymatic degradation. Numerous compounds have been reported to inhibit prion replication and PrPSc accumulation in cell cultures. Among them, we selected 2,2'-biquinoline (BQ) and studied the mechanism of its anti-prion disease activity. Its effect on prion protein (PrP) expression was examined in mouse neuroblastoma (N2a) cells and in prion-infected N2a (ScN2a) cells, using proteinase K (PK) treatment to discriminate between PrPC and PrPSc. We found that BQ time dependently decreased the total amount of PrP and PrP mRNA expression in infected N2a cells, but not uninfected N2a cells. Our results indicate that the inhibition of PrPSc production by BQ was due to a decrease in the total amount of PrP.
