The effect of Fenton reaction on protease-resistant prion protein (PrPSc) degradation and scrapie infectivity

Park, Seok-Joo; Kim, Nam-Ho; Jeong, Byung‐Hoon; Jin, Jae-Kwang; Choi, Joo Hee; Park, Young-Jae; Kim, Jae-Il; Carp, Richard I.; Kim, Yong‐Sun

doi:10.1016/j.brainres.2008.07.117

Cited by 9 publications

(4 citation statements)

References 27 publications

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“…Remediation of prion-contaminated lands poses a challenge; decontamination methods that have been demonstrated to be effective in inactivating prions are difficult to apply in the environment . Several oxidants used in advanced oxidation processes to treat recalcitrant organic contaminants − have been investigated for their ability to degrade PrP TSE including hydrogen peroxide, ozone, − permanganate, − and the Fenton reagent. − Table provides a summary of selected studies that have demonstrated the ability of oxidizing agents to inactivate prions. Most oxidants investigated to date are either insufficiently effective against prions (e.g., H 2 O 2 , permanganate) or possess features that may limit their utility for application to soils (e.g., the gaseous nature of O 3 , low pH needed for optimal application of Fenton reagent).…”

Section: Introductionmentioning

confidence: 99%

Peroxymonosulfate Rapidly Inactivates the Disease-Associated Prion Protein

Chesney

Booth

Lietz

et al. 2016

Environ. Sci. Technol.

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Prions, the etiological agents in transmissible spongiform encephalopathies, exhibit remarkable resistance to most methods of inactivation that are effective against conventional pathogens. Prions are composed of pathogenic conformers of the prion protein (PrPTSE). Some prion diseases are transmitted, in part, through environmental routes. The recalcitrance of prions to inactivation may lead to a persistent reservoir of infectivity that contributes to the environmental maintenance of epizootics. At present, few methods exist to remediate prion-contaminated lands. Here we examined the ability of peroxymonosulfate to degrade PrPTSE as an initial step toward developing an in situ chemical oxidation process to inactivate prions. We find that peroxymonosulfate rapidly degrades PrPTSE from two species. Transition metal-catalyzed decomposition of peroxymonosulfate to produce sulfate radicals appears to enhance degradation. We further demonstrate that exposure to peroxymonosulfate significantly reduced PrPC-to-PrPTSE converting ability as measured by protein misfolding cyclic amplification, used as a proxy for infectivity. Liquid chromatography-tandem mass spectrometry revealed that exposure to peroxymonosulfate results in oxidative modifications to methionine and tryptophan residues. This study indicates that peroxymonosulfate may hold promise for in situ remediation of prion-contaminated surfaces.

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Section: Introductionmentioning

confidence: 99%

Peroxymonosulfate Rapidly Inactivates the Disease-Associated Prion Protein

Chesney

Booth

Lietz

et al. 2016

Environ. Sci. Technol.

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“…The Fenton reaction can induce radical‐mediated damage to both the peptide backbone and side chains of proteins through hydroxylation or direct oxidation of amino acid residues (Stadtman and Berlett, 1997) and may represent a pathway of PrP TSE inactivation in the environment. Fenton reagent induced degradation of PrP TSE (263K, Sc237) in vitro, significantly delayed onset of clinical symptoms (Park et al, 2008) and appeared to effect a 10 6 ‐fold reduction in PrP C ‐to‐PrP TSE converting ability (based on PMCA) (Suyama et al, 2007). In the latter study, untreated positive controls also failed to efficiently amplify, limiting confidence in the PMCA results.…”

Section: Biotic and Abiotic Inactivation Of Prionsmentioning

confidence: 99%

Fate of Prions in Soil: A Review

2011

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Prions are the etiological agents of transmissible spongiform encephalopathies (TSEs), a class of fatal neurodegenerative diseases affecting humans and other mammals. The pathogenic prion protein is a misfolded form of the host-encoded prion protein and represents the predominant, if not sole, component of the infectious agent. Environmental routes of TSE transmission are implicated in epizootics of sheep scrapie and chronic wasting disease (CWD) of deer, elk, and moose. Soil represents a plausible environmental reservoir of scrapie and CWD agents, which can persist in the environment for years. Attachment to soil particles likely influences the persistence and infectivity of prions in the environment. Effective methods to inactivate TSE agents in soil are currently lacking, and the effects of natural degradation mechanisms on TSE infectivity are largely unknown. An improved understanding of the processes affecting the mobility, persistence, and bioavailability of prions in soil is needed for the management of TSE-contaminated environments.

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“…PrP Sc itself is a target of increased oxidative modifications (162), suggesting the presence of chronic oxidative stress in diseased brains. Interestingly, metal-induced oxidative stress has been reported to cause the aggregation and insolubility of PrP C to a form similar to PrP Sc in cell models (12) and to decrease infectivity by causing the hydroxylation and degradation of PrP Sc (164), indicating a role in both the generation and degradation of PrP Sc . Besides, it has been suggested that the conversion of PrP C to PrP Sc involves the formation of a redox-active copper complex within the plasma membrane (125,142,154), supporting the idea that the generation of PrP Sc is facilitated by redox ions.…”

Section: Fig 4 Loss Of Prpmentioning

confidence: 99%

Redox Control of Prion and Disease Pathogenesis

Singh

Das

et al. 2010

Antioxidants & Redox Signaling

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Imbalance of brain metal homeostasis and associated oxidative stress by redox-active metals like iron and copper is an important trigger of neurotoxicity in several neurodegenerative conditions, including prion disorders. Whereas some reports attribute this to end-stage disease, others provide evidence for specific mechanisms leading to brain metal dyshomeostasis during disease progression. In prion disorders, imbalance of brain-iron homeostasis is observed before end-stage disease and worsens with disease progression, implicating ironinduced oxidative stress in disease pathogenesis. This is an unexpected observation, because the underlying cause of brain pathology in all prion disorders is PrP-scrapie (PrP Sc ), a b-sheet-rich conformation of a normal glycoprotein, the prion protein (PrP C ). Whether brain-iron dyshomeostasis occurs because of gain of toxic function by PrP Sc or loss of normal function of PrP C remains unclear. In this review, we summarize available evidence suggesting the involvement of oxidative stress in prion-disease pathogenesis. Subsequently, we review the biology of PrP C to highlight its possible role in maintaining brain metal homeostasis during health and the contribution of PrP Sc in inducing brain metal imbalance with disease progression. Finally, we discuss possible therapeutic avenues directed at restoring brain metal homeostasis and alleviating metal-induced oxidative stress in prion disorders. Antioxid. Redox Signal. 12, 1271-1294.

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The effect of Fenton reaction on protease-resistant prion protein (PrPSc) degradation and scrapie infectivity

Cited by 9 publications

References 27 publications

Peroxymonosulfate Rapidly Inactivates the Disease-Associated Prion Protein

Peroxymonosulfate Rapidly Inactivates the Disease-Associated Prion Protein

Fate of Prions in Soil: A Review

Redox Control of Prion and Disease Pathogenesis

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