Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons

Thomsen, Maj Schneider; Andersen, Morten Højmose; Christoffersen, P; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

doi:10.1016/j.nbd.2015.03.013

Cited by 86 publications

(93 citation statements)

References 48 publications

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“…Dystrophic microglia become more prevalent with human aging and have been found to increase in a variety of diseases including AD [147] and Huntington's disease [148]. There is also evidence that the chronic inflammation that accompanies neurodegeneration leads to local increases in microglia with high iron and ferritin content, possibly due to iron scavenging [149]. The association between increased iron storage and an altered microglia phenotype, particularly a dystrophic one, suggests a possible causative role for iron.…”

Section: Microglia and Agingmentioning

confidence: 99%

Iron, Aging, and Neurodegeneration

Angelova

Brown

2015

Metals

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Abstract:Iron is a trace element of considerable interest to both chemistry and biology. In a biological context its chemistry is vital to the roles it performs. However, that same chemistry can contribute to a more deleterious role in a variety of diseases. The brain is a very sensitive organ due to the irreplaceable nature of neurons. In this regard regulation of brain iron chemistry is essential to maintaining neuronal viability. During the course of normal aging, the brain changes the way it deals with iron and this can contribute to its susceptibility to disease. Additionally, many of the known neurodegenerative diseases have been shown to be influenced by changes in brain iron. This review examines the role of iron in the brain and neurodegenerative diseases and the potential role of changes in brain iron caused by aging.

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Section: Microglia and Agingmentioning

confidence: 99%

Iron, Aging, and Neurodegeneration

Angelova

Brown

2015

Metals

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“…The study demonstrates that during EAE progression iron accumulates in the spinal cord and that accumulation is localized in macrophages and microglia, but not in the astrocytes that can recycle iron efficiently from sites of EAE lesions. Thomsen et al (2015) also demonstrate iron accumulation in macrophages and microglia in a model of excitotoxicity based on the administration of the glutamate agonist ibotenic acid, which also triggers neuroinflammation. Interestingly, the authors also describe an increase of the master iron regulating hormone hepcidin following excitotoxic lesion.…”

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confidence: 71%

Metals and neurodegeneration

Aizenman

Mastroberardino

2015

Neurobiology of Disease

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“…Because ferric iron (Fe 3+ , Fe 2+ ) causes a catalytic Haber-Weiss reaction (O •2 −+ H 2 O 2 →O 2 +•OH+OH−), it is essential for the maintenance of Fe homeostasis to maintain a healthy brain, and Fe-related neurodegenerative disorders can result from both iron accumulation in specific brain regions or defects in its metabolism and/or homeostasis 18. H-ferritin is mostly distributed in neurons, L-ferritin in microglia, and both H- and L-ferritin in oligodendrocytes 20. Neuroferritinopathy is the indirect model to study the connection between ferritin and neurological disorders as an autosomal dominant extra-pyramidal movement disorder caused by mutations in the ferritin light chain gene with the characteristics of iron deposition in the basal ganglia and cavitations 7.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation

Yang

et al. 2016

NSJ

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Objective:To study the possible relationship between amyotrophic lateral sclerosis (ALS) patients and their susceptibility to serum ferritin level elevation.Methods:We searched the PubMed, Springer, Medline, and OVID databases for any-language original research articles relating to serum ferritin levels in ALS patients published between June 2005 and June 2015. The search term used with ‘amyotrophic lateral sclerosis’, ‘ferritins’, ‘ferritin’, ‘iron’, ‘iron stores, ‘iron status, ‘iron intake’, and ‘iron consumption’. The meta-analysis software RevMan 5.0 was used for the heterogeneity test, and to test for the overall effect.Results:Six case-control studies met our inclusion criteria including data from a total of 1813 participants. The mean difference of serum ferritin levels comparing ALS to healthy controls was 69.05 (95% confidence interval: 52.56-85.54; p<0.00001); heterogeneity: p=0.03; I2=50%. The findings indicate homology in the sensitivity analysis. Funnel plot assessment indicated publication bias.Conclusion:Our results suggest that ALS is positively associated with susceptibility to the elevation of serum ferritin levels; however, further evidence is required to support this.

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Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons

Cited by 86 publications

References 48 publications

Iron, Aging, and Neurodegeneration

Iron, Aging, and Neurodegeneration

Metals and neurodegeneration

Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation

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