JBIC Journal of Biological Inorganic Chemistry

, Volume 24, Issue 8, pp 1141–1157 | Cite as

Redox active metals in neurodegenerative diseases

  • Karla Acevedo
  • Shashank Masaldan
  • Carlos M. OpazoEmail author
  • Ashley I. BushEmail author
Mini Review
Part of the following topical collections:
  1. Metal Ions and Degenerative Diseases


Copper (Cu) and iron (Fe) are redox active metals essential for the regulation of cellular pathways that are fundamental for brain function, including neurotransmitter synthesis and release, neurotransmission, and protein turnover. Cu and Fe are tightly regulated by sophisticated homeostatic systems that tune the levels and localization of these redox active metals. The regulation of Cu and Fe necessitates their coordination to small organic molecules and metal chaperone proteins that restrict their reactions to specific protein centres, where Cu and Fe cycle between reduced (Fe2+, Cu+) and oxidised states (Fe3+, Cu2+). Perturbation of this regulation is evident in the brain affected by neurodegeneration. Here we review the evidence that links Cu and Fe dyshomeostasis to neurodegeneration as well as the promising preclinical and clinical studies reporting pharmacological intervention to remedy Cu and Fe abnormalities in the treatment of Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS).


Copper Iron Neurodegeneration 



Alzheimer’s disease


Amyloid precursor protein


Amyotrophic lateral sclerosis


Antioxidant 1 copper chaperone 1




Blood–cerebrospinal fluid barrier


Brain capillary endothelial cells


Central nervous system


Cerebrospinal fluid






Copper-transporter 1


Copper chaperone for SOD1


Cytochrome c oxidase copper chaperone


Divalent metal transporter 1








Iron-responsive element


Iron regulatory proteins


Lewy bodies




Magnetic resonance image


Neurofibrillary tangles


Parkinson’s disease


Reactive oxygen species


Substantia nigra pars compacta


Superoxide dismutase 1




Transferrin receptor 1


Untranslated region



The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. This work was supported by the Australian Research Council (AIB, CO), the National Health and Medical Research Council and the CRC for Mental Health (AIB). Figures 1 and 2 were compiled using images from Servier Medical art.

Compliance with ethical standards

Conflict of interest

Prof. Bush is a shareholder in Prana Biotechnology Ltd, Cogstate Ltd, Brighton Biotech LLC, Grunbiotics Pty Ltd, Eucalyptus Pty Ltd, and Mesoblast Ltd. He is a paid consultant for, and has a profit share interest in, Collaborative Medicinal Development Pty Ltd.


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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  1. 1.Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia

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