Iron In Parkinson's

[ironjustice]

Time-Specific Pattern of Iron Deposition in Different Regions in Parkinson's Disease Measured by Quantitative Susceptibility Mapping
Xiaodi Fu 1, Wenbin Deng 1, Xiangqin Cui 1, Xiao Zhou 2, Weizheng Song 3, Mengqiu Pan 4, Xiao Chi 1, Jinghui Xu 5, Ying Jiang 5, Qun Wang 1, Yunqi Xu Front Neurol
. 2021 Aug 4;12:631210. doi: 10.3389/fneur.2021.631210. eCollection 2021.
PMID: 34421781 PMCID: PMC8371047 DOI: 10.3389/fneur.2021.631210
Abstract
Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

Keywords: hoehn-yahr stage; iron deposition; parkinson's disease; quantitative susceptibility mapping; unified parkinson's disease rating scale.

Copyright © 2021 Fu, Deng, Cui, Zhou, Song, Pan, Chi, Xu, Jiang, Wang and Xu.


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[ironjustice]

Review Mol Neurobiol. 2021 Aug 23. doi: 10.1007/s12035-021-02516-5.
Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson's Disease and Intervention with Turmeric
Zuné Jansen van Rensburg 1, Shameemah Abrahams 1 2, Soraya Bardien 3 4, Colin Kenyon 5 6 7
PMID: 34426907 DOI: 10.1007/s12035-021-02516-5
Abstract
Parkinson's disease (PD) is a movement disorder associated with severe loss of mainly dopaminergic neurons in the substantia nigra. Pathological hallmarks include Lewy bodies, and loss of neuromelanin, due to degeneration of neuromelanin-containing dopaminergic neurons. Despite being described over 200 years ago, the etiology of PD remains unknown. Here, we highlight the roles of reactive oxygen species (ROS), iron, alpha synuclein (α-syn) and neuromelanin in a toxic feedback loop culminating in neuronal death and spread of the disease. Dopaminergic neurons are particularly vulnerable due to decreased antioxidant concentration with aging, constant exposure to ROS and presence of neurotoxic compounds (e.g. ortho-quinones). ROS and iron increase each other's levels, creating a state of oxidative stress. α-Syn aggregation is influenced by ROS and iron but also increases ROS and iron via its induced mitochondrial dysfunction and ferric-reductase activity. Neuromelanin's binding affinity is affected by increased ROS and iron. Furthermore, during neuronal death, neuromelanin is degraded in the extracellular space, releasing its bound toxins. This cycle of events continues to neighboring neurons in the form of a toxic loop, causing PD pathology. The increase in ROS and iron may be an important target for therapies to disrupt this toxic loop, and therefore diets rich in certain 'nutraceuticals' may be beneficial. Turmeric is an attractive candidate, as it is known to have anti-oxidant and iron chelating properties. More studies are needed to test this theory and if validated, this would be a step towards development of lifestyle-based therapeutic modalities to complement existing PD treatments.

Keywords: Alpha-synuclein; Iron; Neuromelanin; Parkinson’s disease; Reactive oxygen species; Toxic feedback loop.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.