Chelators in the treatment of iron accumulation in Parkinson's disease

Ross B Mounsey, Peter Teismann

Research output: Contribution to journalArticle

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Abstract

Iron is an essential element in the metabolism of all cells. Elevated levels of the metal have been found in the brains of patients of numerous neurodegenerative disorders, including Parkinson's disease (PD). The pathogenesis of PD is largely unknown, although it is thought through studies with experimental models that oxidative stress and dysfunction of brain iron homeostasis, usually a tightly regulated process, play significant roles in the death of dopaminergic neurons. Accumulation of iron is present at affected neurons and associated microglia in the substantia nigra of PD patients. This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation of α-synuclein protein, and exacerbate or even cause neurodegeneration. There are various treatments aimed at reversing this pathologic increase in iron content, comprising both synthetic and natural iron chelators. These include established drugs, which have been used to treat other disorders related to iron accumulation. This paper will discuss how iron dysregulation occurs and the link between increased iron and oxidative stress in PD, including the mechanism by which these processes lead to cell death, before assessing the current pharmacotherapies aimed at restoring normal iron redox and new chelation strategies undergoing research.

Original languageEnglish
Article number983245
Number of pages12
JournalInternational journal of cell biology
Volume2012
DOIs
Publication statusPublished - 2012

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Chelating Agents
Parkinson Disease
Iron
Therapeutics
Oxidative Stress
Synucleins
Dopaminergic Neurons
Brain
Microglia
Substantia Nigra
Neurodegenerative Diseases
Oxidation-Reduction
Reactive Oxygen Species
Homeostasis
Cell Death
Theoretical Models
Metals
Neurons
Drug Therapy

Cite this

Chelators in the treatment of iron accumulation in Parkinson's disease. / Mounsey, Ross B; Teismann, Peter.

In: International journal of cell biology, Vol. 2012, 983245, 2012.

Research output: Contribution to journalArticle

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