Iron transport in Parkinson's disease
Section snippets
Oxidative stress in Parkinson's disease
Parkinson's disease (PD) is characterized from a neuropathological standpoint by the degeneration of dopaminergic neurons in the mesencephalon and the presence of intracytoplasmic inclusions called Lewy bodies [1]. Apart from rare inherited forms of the disease, the cause of PD has still not been identified [2]. Several different, though not mutually exclusive, mechanisms may participate in the cascade of events leading to neuronal degeneration in PD [3]. These changes include accumulation of
Iron transport in Parkinson's disease
Several mechanisms may account for iron penetration into the brain (Fig. 1). The best known mechanism involves the binding of iron-loaded transferrin to its receptor and its translocation to the intracellular compartment [14]. This transporter has been found to be expressed at the level of endothelial cells and may account for iron penetration into the brain parenchyma. Transferrin receptors have also been detected on the plasma membrane of neurons and glial cells. Thus, this mechanism may
Unanswered questions about iron metabolism in Parkinson's disease
In most cellular organisms, iron levels are tightly regulated at both transcriptional and post-transcriptional levels. Indeed, intra-cellular free iron is controlled by ferritin, the major iron storage protein. Two cytoplasmic proteins, iron regulatory proteins 1 and 2 (IRP1 and IRP2) control the synthesis of ferritin by binding to a stem-loop structure located in the 5′ untranslated region of ferritin mRNA known as IRE. When the concentration of iron is low, IRPs bind to the IRE which blocks
Conflict of interests
Research contracts not related to the topic of this article with Laboratoires Fournier-Solvay, Laboratoires Pierre Fabre, Institut de recherche International Servier, Eisai Japan Laboratory.
Acknowledgements
I would like to thank Nick Barton for checking the text of the manuscript.
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JWH133 inhibits MPP<sup>+</sup>-induced inflammatory response and iron influx in astrocytes
2020, Neuroscience LettersCitation Excerpt :It is evident that iron accumulated in astrocytes in the SN of PD [18]. Divalent metal transporter-1 (DMT1), a proton-coupled metal-ion transport protein, can carry iron from the extracellular to the cytoplasm [19]. In cannabinoids (Δ9-tetrahydrocannabinol, Δ9-THC)- treated cells, serine phosphorylation of DMT1 was significantly reduced [20].
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Crosstalk between Nrf2 signaling and mitochondrial function in Parkinson's disease
2019, Molecular and Cellular NeuroscienceCitation Excerpt :Recent investigations have delineated dysregulation of different iron homeostasis-related proteins in PD patients that may contribute to iron accumulation. For instance, augmented divalent metal transporter 1 (DMT1/SLC11A2) expression in the SN of PD patients (Hirsch, 2009) and mutations in transferrin (TF, the neuronal iron uptake protein) and ceruloplasmin (CP, an iron export protein) are associated with an increase in PD susceptibility (Ayton et al., 2013; Rhodes et al., 2014). Iron is necessary for the proper mitochondrial function, which is especially critical in cases of energetically demanding DA cells.
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Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor inhibit ferrous iron influx via divalent metal transporter 1 and iron regulatory protein 1 regulation in ventral mesencephalic neurons
2014, Biochimica et Biophysica Acta - Molecular Cell ResearchCitation Excerpt :Previous studies have shown that in the SNpc of PD patients and the MPTP-lesioned mouse model, increased DMT1 + IRE expression is associated with local iron accumulation and DAergic neuron degeneration. In Belgrade rats and mk/mk mice, studies have shown less iron accumulation and a lower susceptibility in DMT1 mutant DAergic neurons after a Parkinsonian toxin injection [16,51]. These data support the importance of DMT1 in iron-mediated neurodegeneration in PD.
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Trasferrin receptor 2 gene regulation by microRNA 221 in SH-SY5Y cells treated with MPP<sup>+</sup> as Parkinson's disease cellular model
2013, Neuroscience ResearchCitation Excerpt :Also in this case unclear literature data are reported. For example, while Mastroberardino et al. (2009) tries to attribute the iron excess in dopaminergic neurons in PD to transferrin/TfR2-mediated mitochondrial iron transport system, Hirsch (2009) supports a critical role for DMT1 in iron-mediated neurodegeneration in PD. TfR2 resulted increased in SH-SY5Y cells treated with MPP+.