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Antioxidants 2014, 3(2), 288-308; doi:10.3390/antiox3020288
Review

Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease

1
, 2,3
 and 1,*
Received: 16 January 2014; in revised form: 13 February 2014 / Accepted: 28 February 2014 / Published: 21 April 2014
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Abstract: Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.
Keywords: amyloid; antioxidant; CJD; chelation; Cu; hydroxyl radical; Mn; oxidative stress; SOD2; superoxide dismutase; therapy; transmissible spongiform encephalopathy amyloid; antioxidant; CJD; chelation; Cu; hydroxyl radical; Mn; oxidative stress; SOD2; superoxide dismutase; therapy; transmissible spongiform encephalopathy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Brazier, M.W.; Wedd, A.G.; Collins, S.J. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease. Antioxidants 2014, 3, 288-308.

AMA Style

Brazier MW, Wedd AG, Collins SJ. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease. Antioxidants. 2014; 3(2):288-308.

Chicago/Turabian Style

Brazier, Marcus W.; Wedd, Anthony G.; Collins, Steven J. 2014. "Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease." Antioxidants 3, no. 2: 288-308.

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