Does cellular iron dysregulation play a causative role in Parkinson’s disease?

Kaur, Deepinder; Andersen, Julie

doi:10.1016/j.arr.2004.01.003

Cited by 123Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismIron Metabolism and Disorders

Does cellular iron dysregulation play a causative role in Parkinson’s disease?

Kaur, Deepinder, Andersen, Julie·2004·Ageing Research Reviews

DOI 10.1016/j.arr.2004.01.003

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Abstract

Selective dopaminergic cell loss in Parkinson's disease is correlated with increased levels of cellular iron. It is still hotly debated as to whether the increase in iron is an upstream event which acts to promote neurodegeneration via formation of oxidative stress or whether iron accumulates as a by-product of the neuronal cell loss. Here we review evidence for loss of iron homeostasis as a causative factor in disease-associated neurodegeneration and the primary players which may be involved. A series of recent studies suggest that iron regulatory proteins (IRPs) coordinate both cellular iron levels and energy metabolism, both of which are disrupted in Parkinson's disease (PD) and may in turn contribute to increased levels of oxidative stress associated with the disease. Iron has also been recently been implicated in promotion of alpha-synuclein aggregation either directly or via increasing levels of oxidative stress suggesting an important role for it in Lewy body formation, another important hallmark of the disease.

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Transgenic overexpression of ferritin H into Parkinson disease model mice reduced oxidative stress.
“When ferritin H was transgenically overexpressed into Parkinson disease (PD) model mice, reduced oxidative stress was found (159).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [159]
Overexpression of ferritin H protects cells from MPTP toxicity.
“In addition, overexpression of ferritin H protected cells from the toxicity of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a drug used to create experimental models of PD) (159).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [159]
Iron may play a role in the pathogenesis of PD, at least in the MPTP model.
“Chelation of “labile iron” also protected cells from this toxicity, suggesting that iron may play a role in the pathogenesis of PD, at least in the MPTP model (159).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [159]
Chelation of labile iron protects cells from MPTP toxicity.
“Chelation of “labile iron” also protected cells from this toxicity, suggesting that iron may play a role in the pathogenesis of PD, at least in the MPTP model (159).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [159]

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Ferritin confers protection against iron-mediated neurotoxicity and ferroptosis through iron chelating mechanisms in MPP+-induced MES23.5 dopaminergic cells
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Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson’s disease
Carroll, C., Zeissler, M., Chadborn, N., Gibson, K., Williams, G. T., Zajicek, J., Morrison, K. E., & Hanemann, C. O. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.05.006 · Cited by 34 · see citing works
Targeting ferroptosis and mitophagy with neutrophil-inspired nanozyme for Parkinson's disease therapy
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Authors: Kaur, D., & Andersen, J.
Affiliations: Buck Institute for Research on Aging (US)
Corresponding author: Andersen, Julie
ORCID: Andersen, Julie
Venue: Ageing Research Reviews
Publisher: Elsevier BV
Published: 2004-07
Volume: 3
Issue: 3
Pages: 327-343
ISSN: 1568-1637 (ISSN-L)
DOI: 10.1016/j.arr.2004.01.003
OpenAlex: W1998032181
Cited by: 123
References: 98
Citations by year: 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 1 · 2014: 2 · 2013: 8 · 2012: 7
FWCI: 1.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Ageing Research Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Aging (AG-12141)
National Institute of Neurological Disorders and Stroke (R01NS041264, NS41264)
Topics: Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords: Parkinson's disease, iron homeostasis, iron regulatory proteins, oxidative stress, dopaminergic neuron loss, neurodegeneration, alpha-synuclein aggregation, Lewy bodies, energy metabolism
MeSH terms: Animals, Homeostasis, Humans, Iron, Mesencephalon, Mitochondria, Models, Biological, Nerve Tissue Proteins, Parkinson Disease, Protein Binding, Oxidative Stress, Neurodegenerative Diseases, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Synucleins, alpha-Synuclein

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Does cellular iron dysregulation play a causative role in Parkinson’s disease?

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