NR AHTL
AU Mange,A.; Nishida,N.; Milhavet,O.; McMahon,H.E.; Casanova,D.; Lehmann,S.
TI Amphotericin B inhibits the generation of the scrapie isoform of the prion protein in infected cultures
QU Journal of Virology 2000 Apr; 74(7): 3135-40
PT journal article
AB 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 about the nature of the responsible agent of these diseases remain, it is clear that a protein called PrPsc plays a central role. PrPsc is a conformational variant of PrPc, the normal host protein. Polyene antibiotics such as amphotericin B have been shown to delay the accumulation of PrPsc and to increase the incubation time of the disease after experimental transmission in laboratory animals. Unlike for Congo red and sulfated polyanions, no effect of amphotericin B has been observed in infected cultures. We show here for the first time that amphotericin B can inhibit PrPsc generation in scrapie-infected GT1-7 and N2a cells. Its activity seems to be related to a modification of the properties of detergent-resistant microdomains. These results provide new insights into the mechanism of action of amphotericin B and confirm the usefulness of infected cultures in the therapeutic research of transmissible spongiform encephalopathies.
MH Amino Acid Sequence; Amphotericin B/*pharmacology; Animal; CHO Cells; Cell Line; Hamsters; Mice; Molecular Sequence Data; PrPsc Proteins/*antagonists & inhibitors; Support, Non-U.S. Gov't
AD Institut de Genetique Humaine, CNRS U.P.R. 1142, 34396 Montpellier Cedex 5, France.
SP englisch
PO USA