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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Crosstalk between Nrf2 signaling and mitochondrial function in Parkinson's disease
2019, Molecular and Cellular NeuroscienceCitation Excerpt :Intriguingly, PD brain iron accumulation in the nigral area is in the form of neuromelanin adducts, which are detected by combined nigrosome-1 and neuromelanin-sensitive magnetic resonance imaging (NM-MRI), has emerged as a method for differential PD diagnosis (Jin et al., 2019; Medeiros et al., 2016). A reported increase in iron deposition is observed both in the nigral microglia and nigral DA neurons; however, given the fact that these results were obtained from the postmortem end-stage PD brains, it is plausible that phagocytized damaged dopaminergic neurons may be the source of iron deposits in microglia (Hirsch, 2009). Previous studies with MPTP-based experimental PD models elucidated the role of iron in exacerbating MPTP toxicity and the putative efficacy of iron chelators, such as lactoferrin, in neuroprotection against MPTP-induced DA neurodegeneration (Xu et al., 2019).
Mitochondrial ferritin suppresses MPTP-induced cell damage by regulating iron metabolism and attenuating oxidative stress
2016, Brain ResearchCitation Excerpt :The results indicated that MPTP increased the iron level of the brain, and the significant upregulation of MtFt could exert protective effects against tissue damage caused by the MPTP-induced iron. The results above and those reported by others indicated that MPTP could cause the accumulation of iron in DA neurons in a PD model (Ayton et al., 2012; Faucheux et al., 1995; Hirsch, 2009). However, the role of MtFt is unclear in PD models induced by MPTP.
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
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