Abstract
The transformation of the cellular prion protein (PrPC) into the infectious form (PrPSc) is implicated in the invariably fatal transmissible spongiform encephalopathies. To identify a mechanism to prevent the undesired PrPC → PrPSc transformation, we investigated the interactions of recombinant prion proteins with a number of potential therapeutic agents which inhibit the PrPSc formation, infectivity, and the accumulation of the misfolded form. We show that the prion aggregates formed in the presence of six compounds have no β-structure, which is typical of the infectious form, and possess considerably higher α-helical content than the normal PrPC. The investigated compounds stimulate the formation of α-helices and the destruction of β-structure. They prevent the transformation of α-helical structure into β-sheets. Probably, this is the reason for the resistance to PrPC → PrPSc transformation in the presence of these compounds. The results may be useful for the future therapy of neurodegenerative diseases.
| Original language | English |
|---|---|
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 344 |
| Issue number | 2 |
| Pages (from-to) | 463-470 |
| Number of pages | 8 |
| ISSN | 0006-291X |
| DOIs | |
| Publication status | Published - 02.06.2006 |
Funding
This work was supported by the Deutsche Luft- und Raumfahrtagentur (DLR, Projektträger Gesundheitsforschung) via Grant 01KO0206, the Deutsche Forschungsgemeinschaft via Grant 436 BUL/18/03/05 and by the DAAD via Grant 415-br-probal/ale-03/17635. D. Georgieva thanks the Alexander von Humboldt Foundation, Bonn, Germany, for providing a Research Fellowship, V-8121/BUL/1073481. The work was also supported by grant of the RiNA GmbH, Berlin. It was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
