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Brain Iron Metabolism Dysfunction in Parkinson’s Disease

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Abstract

Dysfunction of iron metabolism, which includes its uptake, storage, and release, plays a key role in neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s disease, and Huntington’s disease. Understanding how iron accumulates in the substantia nigra (SN) and why it specifically targets dopaminergic (DAergic) neurons is particularly warranted for PD, as this knowledge may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for this disease. In this review, we begin with a brief introduction describing brain iron metabolism and its regulation. We then provide a detailed description of how iron accumulates specifically in the SN and why DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on the possible mechanisms involved in iron-induced cell death of DAergic neurons in the SN. Finally, we present evidence in support that iron chelation represents a plausable therapeutic strategy for PD.

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Acknowledgments

We are deeply grateful to Prof. Yang XL, Fudan University, for his encouragement and critical comments on the manuscript. We thank Dr. Xu HM for revising the manuscript, and Dr. Song N and Dr. Ma ZG for their good suggestions to this paper. This work was supported by grants from the National Foundation of Natural Science of China (81430024, 31271131, 31471114, 31371081), from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2011CB504100), from Ministry of Education of China (20123706110002) and from Excellent Innovative Team of Shandong Province and Taishan Scholars Construction Project.

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  1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao, 266071, China

    Hong Jiang, Jun Wang & Junxia Xie

  2. Neurochemistry Laboratory, Division of Psychiatric Neurosciences and Genetics and Aging Research Unit, Massachusetts General Hospital, Boston, MA, 02114, USA

    Jack Rogers

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  1. Hong Jiang
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  2. Jun Wang
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  3. Jack Rogers
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  4. Junxia Xie
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Correspondence to Hong Jiang or Junxia Xie.

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Jiang, H., Wang, J., Rogers, J. et al. Brain Iron Metabolism Dysfunction in Parkinson’s Disease. Mol Neurobiol 54, 3078–3101 (2017). https://doi.org/10.1007/s12035-016-9879-1

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