NR ATFW
AU Caughey,B.W.
TI The most infectious scrapie particle, neuronal traficking of PrP-RES, and effects of anchorless PrP on scrapie
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-27
PT Konferenz-Vortrag
AB
The following topics will be discussed:
1. Analyses of the most and minimal infectious scrapie particles. Size-based fractionations of fragmented 263K scrapie PrPres aggregates showed that non-fibrillar particles, with masses equivalent to 14-28 PrP molecules, are by far the most infectious particles per unit PrP, while particles smaller than PrP hexamers had no converting activity (Nature, in press).
2. Uptake and neuritic trafficking of PrPres in neuronal cells. Fluorescently labeled, infectious PrPres was used to infect neuronal cells in culture. PrPres aggregates were internalized into intracellular vesicles and transported along neurites to points of contact with other cells, apparently by a relatively non-specific pinocytosis or transcytosis mechanism. These experiments visualize and characterize initial steps associated with scrapie infection and transport within neuronal cells. (J. Neuroscience 25: 5207).
3. Anchorless prion protein results in infectious amyloid disease without clinical scrapie: In TSE diseases the roles that amyloid versus non-amyloid deposits play in brain damage remain critical unresolved issues. In scrapie-infected transgenic mice expressing PrP lacking the GPI membrane anchor, PrPres was deposited as amyloid plaques, rather than the usual non-amyloid PrPres. Although amyloid PrPres induced brain damage reminiscent of Alzheimer's disease, clinical manifestations were minimal. In contrast, combined expression of anchorless and wild-type PrP gave rapid clinical scrapie. This model demonstrates for the first time the role of the role of the PrP GPI anchor in pathogenic effects of prion diseases. (Science 308: 1435)
IN
Die Arbeitsgruppe des Autors fraktionierte PrPsc des 263K-Erregerstammes nach Größen und untersuchten unter anderem die Infektiosität dieser Fraktionen. Die größte Infektiosität besaß die Fraktion der anscheinend nicht fibrillären Aggregate aus 14-28 PrPsc-Molekülen. Bei Aggregaten mit maximal 5 PrPsc-Molekülen lag die Infektiosität unter der Nachweisgrenze.
Der Autor berichtet auch über Zellkulturexperimente, welche die Aufnahme fluoreszierender PrPres in intrazelluläre Vesikel und den Transport durch Neuriten zu Kontaktstellungen zu benachrbarten Neuronen zeigten.
Außerdem berichtet der Autor über den Effekt des GPI-Ankers, der auch schon in Science publiziert wurde [ASLY].
AD B.Caughey, LPVD, NIAID/NIH, Rocky Mountain Laboratories, Hamilton, MT 59840 USA
SP englisch
PO Deutschland