Aceruloplasminemia

Roberti, Maria do Rosário Ferraz; Filho, Handel Meireles Borges; Gonçalves, Cláudio Humberto; Lima, Flávio Leão

doi:10.5581/1516-8484.20110104

Cited by 31 publications

(8 citation statements)

References 17 publications

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“…As it was mentioned above, by binding to Cp, copper stimulates its ferroxidase activity and participates in iron homeostasis, so it may be hypothesized that some indirect toxicity mediated by altered iron concentrations may be a consequence of low copper levels. Accordingly, aceruloplasmemia, an autosomal recessive disease characterized by Cp deficiency and caused by mutations in the CPN gene, is associated with iron accumulation in the pancreas, liver, basal ganglia, and retina [217]. In addition, brain iron accumulation has been reported to be associated with the loss of neurons in the same regions, and the effects appear be associated with the ability of ferrous ions to enhance oxidative stress conditions.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications

Gromadzka

Tarnacka

Flaga

et al. 2020

IJMS

204

115

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Copper is one of the most abundant basic transition metals in the human body. It takes part in oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining the integrity of blood vessels, as well as in iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cell signaling and may participate in modulation of membrane receptor-ligand interactions, control of kinase and related phosphatase functions, as well as many cellular pathways. Its role is also important in controlling gene expression in the nucleus. In the nervous system in particular, copper is involved in myelination, and by modulating synaptic activity as well as excitotoxic cell death and signaling cascades induced by neurotrophic factors, copper is important for various neuronal functions. Current data suggest that both excess copper levels and copper deficiency can be harmful, and careful homeostatic control is important. This knowledge opens up an important new area for potential therapeutic interventions based on copper supplementation or removal in neurodegenerative diseases including Wilson’s disease (WD), Menkes disease (MD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. However, much remains to be discovered, in particular, how to regulate copper homeostasis to prevent neurodegeneration, when to chelate copper, and when to supplement it.

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Section: Parkinson's Diseasementioning

confidence: 99%

Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications

Gromadzka

Tarnacka

Flaga

et al. 2020

IJMS

204

115

View full text Add to dashboard Cite

show abstract

“…The use of a chelating agent, such as oral deferiprone (DFP), was shown to be protective against the increased oxidative stress and retinal degeneration ( Hadziahmetovic et al, 2011 ; Wolkow et al, 2012 ). Despite the good results obtained in the mouse model, the use of DFP on a patient resulted in a worsening of symptoms ( Mariani et al, 2004 ), while variable results ranging from mild amelioration to no effect on neurological symptoms were obtained in patients treated with deferasirox ( Skidmore et al, 2008 ; Roberti Mdo et al, 2011 ). However iron-chelating therapy appeared effective in reducing the hepatic and pancreatic iron overload ( Finkenstedt et al, 2010 ).…”

Section: Nbia Caused By Defects In Genes Coding For Proteins Of Iron mentioning

confidence: 99%

Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms

2014

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Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer's and Parkinson's disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited.The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

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“…The effectiveness of iron chelation therapy has been described in previous reports ( 8 , 19 - 21 ). Additionally, some reports have suggested that iron chelation therapy is effective for hepatic iron overload, diabetes mellitus, and neurological symptoms, but not for improving iron accumulation, which can be observed on brain MRI ( 15 , 22 , 23 ). In our case, the AST and ALT levels were found to be elevated at the time of her first visit to the Department of Gastroenterology, and phlebotomy therapy and the discontinuation of oral iron supplements were carried out to treat her liver hemosiderosis.…”

Section: Discussionmentioning

confidence: 99%

Aceruloplasminemia with Abnormal Compound Heterozygous Mutations Developed Neurological Dysfunction during Phlebotomy Therapy

et al. 2018

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Aceruloplasminemia is an autosomal recessive inherited disorder caused by ceruloplasmin gene mutations. The loss of ferroxidase activity of ceruloplasmin due to gene mutations causes a disturbance in cellular iron transport. We herein describe a patient with aceruloplasminemia, who presented with diabetes mellitus that was treated by insulin injections, liver hemosiderosis treated by phlebotomy therapy, and neurological impairment. A genetic analysis of the ceruloplasmin gene revealed novel compound heterozygous mutations of c.1286_1290insTATAC in exon 7 and c.2185delC in exon 12. This abnormal compound heterozygote had typical clinical features similar to those observed in aceruloplasminemia patients with other gene mutations.

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Aceruloplasminemia

Cited by 31 publications

References 17 publications

Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications

Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications

Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms

Aceruloplasminemia with Abnormal Compound Heterozygous Mutations Developed Neurological Dysfunction during Phlebotomy Therapy

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