TY - JOUR
T1 - Congo red analogues as potential anti-prion agents
AU - Villa, Stefania
AU - Cignarella, Giorgio
AU - Barlocco, Daniela
AU - Gervasoni, Marco
AU - Carcassola, Gabriella
AU - Giannino, Laura
AU - Mantegazza, Paolo
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 'Transmissible Spongiform Encephalopathies' (TSE) are a group of degenerative, progressive and fatal disorders of CNS which affect both humans and animals, characterised by a long incubation time. The pathogenetic mechanism in TSE is the conversion of normal prion protein (PrPsen) to an altered protease resistant isoform (PrPres) that accumulates in amyloid deposits into the brain; therefore, PrPres is the primary target for therapeutic strategies. The discovery that the sulphonated azo dye Congo red (CR) is able to inhibit the replications of TSE agents and the accumulation of PrPres in animals and in scrapie infected mouse neuroblastoma cells induced us to designe molecules structurally related to CR (1a-f, 2f,g). The compounds were tested in vitro to evaluate their interaction with 263K PrPres. Six of the tested compounds were found to interact with PrPres molecules and to over-stabilise the PrPres aggregates, as CR does. However, none of them induced the reversion of PrP res to PrPsen.
AB - 'Transmissible Spongiform Encephalopathies' (TSE) are a group of degenerative, progressive and fatal disorders of CNS which affect both humans and animals, characterised by a long incubation time. The pathogenetic mechanism in TSE is the conversion of normal prion protein (PrPsen) to an altered protease resistant isoform (PrPres) that accumulates in amyloid deposits into the brain; therefore, PrPres is the primary target for therapeutic strategies. The discovery that the sulphonated azo dye Congo red (CR) is able to inhibit the replications of TSE agents and the accumulation of PrPres in animals and in scrapie infected mouse neuroblastoma cells induced us to designe molecules structurally related to CR (1a-f, 2f,g). The compounds were tested in vitro to evaluate their interaction with 263K PrPres. Six of the tested compounds were found to interact with PrPres molecules and to over-stabilise the PrPres aggregates, as CR does. However, none of them induced the reversion of PrP res to PrPsen.
KW - Anti-prion-molecules
KW - Congo red
KW - Transmissible spongiform encephalopathies (TSE)
UR - http://www.scopus.com/inward/record.url?scp=0141788017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141788017&partnerID=8YFLogxK
U2 - 10.1016/S0014-827X(03)00151-4
DO - 10.1016/S0014-827X(03)00151-4
M3 - Article
C2 - 13679188
AN - SCOPUS:0141788017
VL - 58
SP - 929
EP - 937
JO - Farmaco
JF - Farmaco
SN - 0014-827X
IS - 9
ER -