Congo red inhibition of scrapie agent replication

Caughey, Byron; Ernst, Darwin; Race, Richard E.

doi:10.1128/jvi.67.10.6270-6272.1993

Cited by 122 publications

(37 citation statements)

References 24 publications

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“…Our results therefore failed to show any evidence that quinacrine offers benefit when using the simple but objective measure of survival prolongation in an in vivo model of mouse‐adapted CJD. This was somewhat unexpected given that previous studies of Congo Red,15, 16 selected sulfated polyanions,12, 17 and certain tetrapyrroles5, 18 have demonstrated reasonably good concordance between in vitro antiprion potency (using cell‐based assays of the inhibition of PrP sc production or its enhanced clearance) and their in vivo efficacy in animal studies. The reasons for such lack of correlation for quinacrine are unknown but are unlikely to relate to the inability to penetrate the blood–brain barrier, as suggested for the poor therapeutic effects of sulfated polyanions when used late in the incubation phase of rodent TSE models 12, 18.…”

Section: Discussionmentioning

confidence: 92%

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

Collins

Lewis

Brazier

et al. 2002

Annals of Neurology

142

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Paramount among issues relating to the transmissible spongiform encephalopathies (also known as prion diseases) is the absence of any effective therapy. This need has been heightened by the substantial European and emerging global problem of bovine spongiform encephalopathy and consequent variant Creutzfeldt-Jakob disease. Stimulated by the recent reports of a potent antiprion effect in cell culture-based clearance assays, we studied the utility of quinacrine in a well-characterized in vivo model of mouse-adapted transmissible spongiform encephalopathy. Our results failed to show any evidence that quinacrine is effective when using the simple but objective measure of survival prolongation.

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Section: Discussionmentioning

confidence: 92%

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

Collins

Lewis

Brazier

et al. 2002

Annals of Neurology

142

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“…Congo red, however, is highly toxic, metabolizes to carcinogenic products and is not able to cross the blood–brain barrier. Because of the structural similarity and similar inhibition potency in cell‐based assays (Caughey et al. 1993, 2003) between Congo red and the non‐toxic compound curcumin some of the proposed mechanisms might also be applicable to the latter compound.…”

Section: Discussionmentioning

confidence: 99%

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

Hafner-Bratkovič

Gašperšič

Šmid

et al. 2007

Journal of Neurochemistry

126

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J. Neurochem. (2008) 104, 1553–1564. 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.

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“…2001a). In addition, sulfated sugars were shown to inhibit the accumulation of PrP Sc in scrapie infected neuroblastoma cells (Caughey et al . 1993; Caughey and Raymond 1993; Gabizon et al .…”

Section: Heparin Blocks the Binding Of Prpsc Aggregates To Nmsmentioning

confidence: 99%

The binding of prion proteins to serum components is affected by detergent extraction conditions

Shaked¹,

Engelstein²,

Gabizon³

2002

Journal of Neurochemistry

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As many GPI anchored proteins, PrP C and its abnormal conformer PrP Sc , are inserted into membrane microdomains known as rafts. Upon raft disruption, PrP C becomes soluble, while PrP Sc aggregates into insoluble structures. It was recently published that, as opposed to PrP C , PrP Sc , as well as its protease resistant core PrP27-30, can bind specifically to plasminogen and other serum components. These findings were suggested to have important physiological implications in transmissible spongiform encephalopathies (TSE) diagnosis and pathogenesis. In this work, we show that the binding of PrP Sc or PrP 27-30 to serum proteins occurs only at specific detergent combinations, in which disease associated PrPs are present in aggregated structures. At detergent conditions in which rafts are intact, it is actually PrP C. that binds to blood proteins, albeit not directly, but through neighboring rafts components. Our results therefore indicate that the binding of PrP Sc to blood components has no physiological relevance.

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Congo red inhibition of scrapie agent replication

Cited by 122 publications

References 24 publications

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

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

The binding of prion proteins to serum components is affected by detergent extraction conditions

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Congo red inhibition of scrapie agent replication

Cited by 122 publications

References 24 publications

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model

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

The binding of prion proteins to serum components is affected by detergent extraction conditions

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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 PrP^Sc accumulation