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

Antioxidants
Marcus W BrazierSteven J Collins

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.

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Citations

Sep 24, 2016·Journal of Huntington's Disease·Amit Kumar, Rajiv R Ratan
Jan 9, 2020·The International Journal of Neuroscience·Maria Bandookwala, Pinaki Sengupta
Sep 29, 2019·Current Medicinal Chemistry·Carlo MustazzaCarla Raggi

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Methods Mentioned

BETA
chemical modification
protein knockout
glycosylation

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