Metal attenuating therapies in neurodegenerative disease

Abstract

The clinical and pathological spectrum of neurodegenerative diseases is diverse, although common to many of these disorders is the accumulation of misfolded proteins, with oxidative stress thought to be an important contributing mechanism to neuronal damage. As a corollary, transition metal ion dyshomeostasis appears to play a key pathogenic role in a number of these maladies, including the most common of neurodegenerative diseases. In this review, studies spanning a wide variety of neurodegenerative disorders are presented with their involvement of transition metals compared and contrasted, including more detailed treatise in relation to Alzheimer’s disease, Parkinson’s disease and prion diseases. For each of these diseases, a discussion of the evolving scientific rationale for the development of therapies aimed at ameliorating the detrimental effects of transition metal dysregulation, including results from various human trials, is then provided.

Keywords::

• Alzheimer’s disease
• amyloid
• brain
• chelator
• clioquinol
• copper
• hydroxyl radical
• manganese
• MPAC
• oxidative stress
• Parkinson’s disease
• PBT2
• prion

Acknowledgement

The authors wish to thank the Victorian Brain Bank for providing the stained tissue sections displayed in this article.

Financial & competing interests disclosure

SJ Collins is the beneficiary of a NH & MRC Practitioner Fellowship #APP 1005826 and AG Wedd is supported by an ARC grant #DP 1093345. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.