IngentaConnect Curcumin binds to the -helical intermediate and to the amyloid fo...

Authors: Hafner-Bratkovič, Iva¹; Gašperšič, Jernej¹; Šmid, Lojze M.; Bresjanac, Mara; Jerala, Roman¹

Source: Journal of Neurochemistry, Volume 104, Number 6, March 2008 , pp. 1553-1564(12)

Abstract:

Conversion of the native, predominantly α-helical conformation of prion protein (PrP) into the β-stranded conformation is characteristic for the transmissible spongiform encephalopathies such as Creutzfeld-Jakob disease. Curcumin, an extended planar molecule and a dietary polyphenol, inhibits in vitro conversion of PrP and formation of protease resistant PrP in neuroblastoma cell lines. Curcumin recognizes the converted β-form of the PrP both as oligomers and fibrils but not the native form. Curcumin binds to the prion fibrils in the left-handed chiral arrangement as determined by circular dichroism. We show that curcumin labels the plaques of the brain sections of variant Creutzfeld-Jakob disease cases and stains the same structures as antibodies against the PrP. In contrast to thioflavin T, curcumin also binds to the α-helical intermediate of PrP present at acidic pH at stoichiometry of 1 : 1. Congo red competes with curcumin for binding to the α-intermediate as well as to the β-form of PrP but is toxic and binds also to the native form of PrP. We therefore show that the partially unfolded structural intermediate of the PrP can be targeted by non-toxic compound of natural origin.

Keywords: amyloid; Congo red; curcumin; intermediate; oligomer; prion

Document Type: Research article

DOI: 10.1111/j.1471-4159.2007.05105.x

Affiliations: 1: Department of Biotechnology, National Institute of Chemistry, School of Medicine, University of Ljubljana, Slovenia

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Curcumin binds to the α-helical intermediate and to the amyloid form of prion protein - a new mechanism for the inhibition of PrPSc accumulation

Curcumin binds to the α-helical intermediate and to the amyloid form of prion protein - a new mechanism for the inhibition of PrP^Sc accumulation