Next Article in Journal
A Quantum Chemical and Statistical Study of Phenolic Schiff Bases with Antioxidant Activity against DPPH Free Radical
Previous Article in Journal
Antioxidant and Free Radical Scavenging Capacity of Seed and Shell Essential Oils Extracted from Abrus precatorius (L)
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,*
1 Department of Pathology, University of Melbourne, Parkville, VIC 3010, Australia 2 The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia 3 School of Chemistry, The University of Melbourne, Victoria 3010, Australia
* Author to whom correspondence should be addressed.
Received: 16 January 2014 / Revised: 13 February 2014 / Accepted: 28 February 2014 / Published: 21 April 2014
View Full-Text   |   Download PDF [838 KB, uploaded 21 April 2014]   |   Browse Figures

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.

Share & Cite This Article

Export to BibTeX |
EndNote


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.

View more citation formats

Article Metrics

Comments

Citing Articles

[Return to top]
Antioxidants EISSN 2076-3921 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert