Oxidative damage to nucleic acids in human prion disease

Marin Guentchev; Sandra L. Siedlak; Christa Jarius; Fabrizio Tagliavini; Rudy J. Castellani; George Perry; Mark A. Smith; Herbert Budka

doi:10.1006/nbdi.2002.0477

Oxidative damage to nucleic acids in human prion disease

Marin Guentchev, Sandra L. Siedlak, Christa Jarius, Fabrizio Tagliavini, Rudy J. Castellani, George Perry, Mark A. Smith, Herbert Budka^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

Recently, several studies proposed a physiological role for the cellular prion protein (PrP^c) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrP^c homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrP^c plays a key role in the pathogenesis of these disorders.

Original language	English (US)
Pages (from-to)	275-281
Number of pages	7
Journal	Neurobiology of Disease
Volume	9
Issue number	3
DOIs	https://doi.org/10.1006/nbdi.2002.0477
State	Published - 2002

Funding

This work was supported by the Austrian Science Fund (Project No. P-14584), is part of the European Union Concerted Action “Human transmissible spongiform encephalopathies (prion diseases): the neuropathology network (PRIONET)” (Project leader: H. Budka), and was supported by and grants from the National Institutes of Health and the Alzheimer’s Association.

ASJC Scopus subject areas

Neurology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1006/nbdi.2002.0477

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title = "Oxidative damage to nucleic acids in human prion disease",

abstract = "Recently, several studies proposed a physiological role for the cellular prion protein (PrPc) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrPc homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrPc plays a key role in the pathogenesis of these disorders.",

author = "Marin Guentchev and Siedlak, {Sandra L.} and Christa Jarius and Fabrizio Tagliavini and Castellani, {Rudy J.} and George Perry and Smith, {Mark A.} and Herbert Budka",

note = "Funding Information: This work was supported by the Austrian Science Fund (Project No. P-14584), is part of the European Union Concerted Action “Human transmissible spongiform encephalopathies (prion diseases): the neuropathology network (PRIONET)” (Project leader: H. Budka), and was supported by and grants from the National Institutes of Health and the Alzheimer{\textquoteright}s Association.",

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AU - Guentchev, Marin

AU - Siedlak, Sandra L.

AU - Jarius, Christa

AU - Tagliavini, Fabrizio

AU - Castellani, Rudy J.

AU - Perry, George

AU - Smith, Mark A.

AU - Budka, Herbert

N1 - Funding Information: This work was supported by the Austrian Science Fund (Project No. P-14584), is part of the European Union Concerted Action “Human transmissible spongiform encephalopathies (prion diseases): the neuropathology network (PRIONET)” (Project leader: H. Budka), and was supported by and grants from the National Institutes of Health and the Alzheimer’s Association.

PY - 2002

Y1 - 2002

N2 - Recently, several studies proposed a physiological role for the cellular prion protein (PrPc) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrPc homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrPc plays a key role in the pathogenesis of these disorders.

AB - Recently, several studies proposed a physiological role for the cellular prion protein (PrPc) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrPc homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrPc plays a key role in the pathogenesis of these disorders.

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Oxidative damage to nucleic acids in human prion disease

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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