TY - JOUR
T1 - Interactions of recombinant prions with compounds of therapeutical significance
AU - Georgieva, Dessislava
AU - Schwark, Daniel
AU - von Bergen, Martin
AU - Redecke, Lars
AU - Genov, Nicolay
AU - Betzel, Christian
N1 - Funding Information:
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.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/6/2
Y1 - 2006/6/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33646105864&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.03.135
DO - 10.1016/j.bbrc.2006.03.135
M3 - Journal articles
C2 - 16630566
AN - SCOPUS:33646105864
SN - 0006-291X
VL - 344
SP - 463
EP - 470
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
