NR AWLC
AU Nordström,E.K.; Luhr,K.M.; Ibanez,C.; Kristensson,K.
TI Cellular levels of PrPsc are affected by interventions with the MEK1/2 pathway in prion-infected GT1-1 cells
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-36
PT Konferenz-Poster
AB The conversion of the normal cellular prion protein, PrPc, to PrPsc may be facilitated by various factors, which remain to be further characterized. In the present study we demonstrate that brainderived neurotrophic factor (BDNF), a growth factor of the neurotrophin family, stimulates formation of PrPsc in a gonadotropin-releasing hormone-secreting neuronal cell line (GT1-1 cells). We also found that the prion-infected cells can be completely cleared from PrPsc by treatment with inhibitors of MEK1/2, a component of one of the intracellular signaling pathways activated by BDNF. The MEK1/2 inhibitors were also efficient in clearing PrPsc from prion-infected GT1-1 cells stimulated to accumulate high levels of PrPsc by enhanced serum concentrations in the medium or by the use of the serum-free, neuron specific neurobasal medium. The neurobasal medium contains Zn and we observed that Zn increases the amounts of PrPsc in scrapie-infected GT1-1 cells. Zn acts as a cofactor for protein structure (zinc-finger proteins), serves as the catalytic site of many metalloproteins, increases aggregation of amyloid and modulates synaptic activities, but it can also activate the MEK pathway. We conclude that factors, which can activate the MEK1/2 pathway such as BDNF and Zn, may increase levels of PrPsc, and, conversely, that inhibitors of the MEK1/2 pathway can clear PrPsc from prion-infected cells. The MEK1/2 pathway may therefore be a potential target for therapeutic intervention in prion diseases. This research was supported by EC grant EU LSHB-CT-2006-019090 and Stiftelsen Sigurd och Elsa Goljes minne.
AD Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. E-mail: Elin.Nordstrom@ki.se
SP englisch
PO Italien