The Relevance of Iron in the Pathogenesis of Parkinson's Disease

Götz, Mario E.; Double, Kay L.; Gerlach, Manfred; Youdim, Moussa B. H.; Riederere, Peter

doi:10.1196/annals.1306.017

Cited by 282 publications

(167 citation statements)

References 119 publications

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“…Abnormally high levels of iron seen at autopsy are associated with nigral degeneration in PD and increase with the severity of neuropathologic changes (9,221). Although increased iron could signal a primary role of oxidative stress in PD pathology, iron overload could alternatively be a consequence of sequestration by eosinophilic protein aggregates.…”

Section: Role Of Oxidative Stress In the Pathogenesis Of Pd And Modelmentioning

confidence: 99%

Oxidative Stress and Neurotoxicity

Sayre

Perry

Smith

2007

Chem. Res. Toxicol.

754

494

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There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.

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Section: Role Of Oxidative Stress In the Pathogenesis Of Pd And Modelmentioning

confidence: 99%

Oxidative Stress and Neurotoxicity

Sayre

Perry

Smith

2007

Chem. Res. Toxicol.

754

494

View full text Add to dashboard Cite

show abstract

“…However, postmortem evidence of increased iron content in the SN of parkinsonian brain [7] has suggested that the generation of reactive oxygen species, possibly facilitated by iron, may be responsible for cellular damage and the subsequent cell death. Others have suggested that iron levels increase with the progression of PD [8] .…”

Section: Introductionmentioning

confidence: 99%

Determination of brain iron content in patients with Parkinson’s disease using magnetic susceptibility imaging

et al. 2009

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Objective To compare the phase radians in several cerebral regions between patients with Parkinson's disease (PD) and control subjects, and to evaluate whether iron deposition quantified by susceptibility-weighted imaging (SWI) is related to the severity of motor symptoms of PD. Methods SWI consisted of both magnitude and phase images from a fully flow-compensated, 3-dimensional and gradient-echo (GRE) sequence. Magnitude and phase data were collected at GE HD 1.5T.The regions evaluated included frontal white matter, grey matter, cerebrospinal fluid, putamen, caudate nucleus (CN), substantia nigra pars compacta (SNc), substantia nigra pars reticulata (SNr), and red nucleus (RN). A total number of 42 patients (12 patients without cognitive dysfunction, and 30 with cognitive dysfunction from mild to moderate degrees) and 30 control subjects were employed in the present study. Results The phase radians of SNc, CN and RN in PD patients were lower than those in control subjects (P<0.05). Conclusion The phase radians can be used to estimate the brain iron deposition in PD patients, which may be helpful in the diagnosis and longitudinal monitoring of PD.

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“…A growing body of evidence suggests that iron accumulation plays a key role in the etiology and pathology of neurodegenerative diseases, such as Parkinson's disease (Gotz et al, 2004;Berg and Hochstrasser, 2006). However, the underlying mechanisms of iron accumulation have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…However, excess iron can generate highly reactive hydroxyl radicals ( OH) by the Fenton reaction (Stohs and Bagchi, 1995), which can damage proteins, lipids and DNA. Recently many literatures have confirmed that iron plays a key role in Parkinson's disease (PD) and other neurodegenerative diseases (Gotz et al, 2004;Wang et al, 2004Wang et al, , 2007Youdim et al, 2004;Berg and Hochstrasser, 2006;Jiang et al, 2006Jiang et al, , 2007. Increased iron content was found in the substantia nigra pars compacta (SNpc) of parkinsonian brains (Atasoy et al, 2004;Gerlach et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Over-expressed human divalent metal transporter 1 is involved in iron accumulation in MES23.5 cells

Jiang

Wang

et al. 2008

Neurochemistry International

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Elevated iron accumulation has been reported in brain regions in some neurodegenerative disorders. However, the mechanism for this is largely unknown. Divalent metal transporter 1 (DMT1) is an important divalent cation transporter. The aim of the present study is to construct recombinant adenovirus encoding human DMT1 with iron responsive element (DMT1 + IRE) and infect MES23.5 dopaminergic cells in order to investigate the relationship between increased DMT1 + IRE expression and iron accumulation. The human DMT1 gene was obtained by RT-PCR from tissues of human duodenum. AdDMT1 + IRE was successfully constructed and identified by PCR, restriction endonuclease analyses and DNA sequencing, respectively. It was able to efficiently infect MES23.5 cells, which was confirmed by RT-PCR and Western blots. When incubated with 100 mM ferrous iron for 6 h, the intracellular iron levels dramatically increased in AdDMT1 + IRE infected MES23.5 cells compared to the solely adenovirus infected cells. Meanwhile, the levels of hydroxyl free radicals and malondialdehyde (MDA) in these cells increased. This led to the activation of caspase-3. The apoptosis in AdDMT1 + IRE infected cells was shown with hypercondensed nuclei using Hoechst staining. Analysis of DNA extracted from these cells showed the typical ''ladder pattern'', indicating the formation of mono-and oligonucleosomes. These results suggested that increased DMT1 + IRE expression in MES23.5 cells caused the increased intracellular iron accumulation. This resulted in the increased oxidative stress leading to ultimate cell apoptosis. #

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The Relevance of Iron in the Pathogenesis of Parkinson's Disease

Cited by 282 publications

References 119 publications

Oxidative Stress and Neurotoxicity

Oxidative Stress and Neurotoxicity

Determination of brain iron content in patients with Parkinson’s disease using magnetic susceptibility imaging

Over-expressed human divalent metal transporter 1 is involved in iron accumulation in MES23.5 cells

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