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The neurotoxicity of iron, copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.

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Abbreviations

AP-1:

Activator protein-1

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CoCl2 :

Cobalt chloride

DMT1:

Divalent metal transporter 1

GLT-1:

Glutamate transporter-1

GSH:

Glutathione

HIF-1α:

Hypoxia inducible factor 1α

IL-6:

Interleukin-6

IREs:

Iron-responsive elements

MAPK:

Mitogen-activated protein kinase

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mTOR:

Mechanistic target of rapamycin

NAC:

N-acetyl-l-cysteine

NO:

Nitric oxide

NorSAL:

Norsalsolinol

NOS:

Nitric oxide synthase

6-OHDA:

6-Hydroxydopamine  

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SAL:

Salsolinol

SNpc:

Substantia nigra pars compacta

SOD:

Superoxide dismutase

THP:

Tetrahydropapaveroline

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Acknowledgments

The authors gratefully acknowledge the National Natural Science Foundation of China (Grant No. 11375213, 21390411), National Basic Research Program of China (Grant No. 2011CB933101), Hundred Talents Program of the Chinese Academy of Sciences.

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Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, 100049, China

    A. P. Lan, J. Chen, Z. F. Chai & Y. Hu

  2. School of Radiological and Interdisciplinary Sciences, Soochow University, Suzhou, 215123, China

    Z. F. Chai

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  1. A. P. Lan
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  2. J. Chen
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  4. Y. Hu
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Lan, A.P., Chen, J., Chai, Z.F. et al. The neurotoxicity of iron, copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms. Biometals 29, 665–678 (2016). https://doi.org/10.1007/s10534-016-9942-4

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