The Role of Iron in the Pathogenesis of Parkinsons Disease

Manfred Gerlach,1 Kay L. Double,2 Mario E. Götz,3 Moussa B. H. Youdim,4 and Peter Riederer5

1 Department of Child and Adolescence Psychiatry and Psychotherapy, Clinical Neurochemistry, University of Würzburg, Füchsleinstrasse 15, D-97080 Würzburg, Germany <[email protected]>

2Prince of Wales Medical Research Institute, Barker St., Randwick, Sydney, NSW, 2031, Australia

<[email protected]>

3Department of Pharmacology, Universitätsklinikum Kiel, Hospitalstrasse 4, D-24105 Kiel, Germany <[email protected]>

4Eve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, and Department of Pharmacology, Technion-Faculty of Medicine, Efron St., PO Box 969-7, Haifa 31096, Israel < [email protected] >

5Department of Psychiatry and Psychotherapy, Clinical Neurochemistry, National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, University of Würzburg, Füchsleinstrasse 15, D-97080 Würzburg, Germany <[email protected]>

1 INTRODUCTION 126

2 IRON IN THE ETIOLOGY OF PARKINSON'S DISEASE 128

2.1 Epidemiological Findings 128

2.2 Genetic Disorders Implicated with Misregulation of Iron Metabolism and Parkinsonism 128

2.3 Brain Iron in Parkinson's Disease 130

3 SOURCES OF INCREASED IRON IN PARKINSON'S DISEASE 133

3.1 Ferritin 134

3.2 Neuromelanin 137

Metal Ions in Life Sciences, Volume 1 Edited by Astrid Sigel, Helmut Sigel and Roland K. O. Sigel © 2006 John Wiley & Sons, Ltd

4 CONSEQUENCES OF IRON OVERLOAD IN PARKINSON'S

DISEASE 139

4.1 Oxidative Stress-induced Neuronal Damage 139

4.2 Protein Aggregation 140 5 GENERAL CONCLUSIONS 141

ACKNOWLEDGMENTS 142

ABBREVIATIONS AND DEFINITIONS 142

REFERENCES 143

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