Oxylipin Profiles in Plasma of Patients with Wilson’s Disease

Azbukina, Nadezhda V.; Лопачев, А. В.; Chistyakov, Dmitry V.; Goriainov, Sergei V.; Astakhova, A. A.; Poleshuk, Vsevolod V.; Kazanskaya, Rogneda B.; Федорова, Т. Н.; Sergeeva, Marina G.

doi:10.3390/metabo10060222

Cited by 13 publications

(5 citation statements)

References 48 publications

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“…In patients with neurological symptoms, increased serum levels of lipid peroxidation and reactive oxygen species (ROS) markers, such as malondialdehyde (MDA) and glutamate, along with cytokines (IL6, IL8, IL10, and TNF-α) have been described [ 141 ]. In addition, a profile of polyunsaturated fatty acids named oxylipins was differentially detected in WD patients, which act as mediators in oxidative stress injury and inflammation [ 142 ]. Consequently, these analytes could potentially be used to assess the progression of neurological symptoms.…”

Section: The Need For Biomarkers For a Better Diagnosismentioning

confidence: 99%

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

et al. 2021

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Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD’s phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.

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Section: The Need For Biomarkers For a Better Diagnosismentioning

confidence: 99%

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

et al. 2021

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“…WD is a rare autosomal recessive disease, caused by mutations in the copper-transporting P-type ATPase-encoding gene ATP7B responsible for the transport of copper into bile from hepatocytes [ 126 ]. Mutations in this gene lead to the accumulation of toxic copper in various tissues and organs, priming for chronic liver disease, CNS abnormalities and psychiatric disturbances.…”

Section: Lipid*omic*s In Rare Diseasesmentioning

confidence: 99%

“…It has been shown that oxylipins are deeply involved in the regulation of inflammatory processes by evoking anti-inflammatory and pro-resolving mechanisms [ 127 ]. Establishing the oxylipin profiles of WD and healthy controls, using the patient’s plasma, revealed an increase in eight oxylipins in WD compared to the controls, indicating an involvement of oxidative stress damage, inflammation and peroxisome proliferator-activated receptor (PPAR) signaling pathways [ 126 ].…”

Section: Lipid*omic*s In Rare Diseasesmentioning

confidence: 99%

Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases

Zandl-Lang

Plecko

Köfeler

2023

IJMS

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Even though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents specific treatment, as well as genetic counseling for further family planning. Increasing the diagnostic rate and reducing the time to diagnosis in children with unclear disease are crucial for a better patient outcome and improvement of quality of life. In many cases, NGS reveals variants of unknown significance (VUS) that need further investigations. The delineation of novel (lipid) biomarkers is not only crucial to prove the pathogenicity of VUS, but provides surrogate parameters for the monitoring of disease progression and therapeutic interventions. Lipids are essential organic compounds in living organisms, serving as building blocks for cellular membranes, energy storage and signaling molecules. Among other disorders, an imbalance in lipid homeostasis can lead to chronic inflammation, vascular dysfunction and neurodegenerative diseases. Therefore, analyzing lipids in biological samples provides great insight into the underlying functional role of lipids in healthy and disease statuses. The method of choice for lipid analysis and/or huge assemblies of lipids (=lipidome) is mass spectrometry due to its high sensitivity and specificity. Due to the inherent chemical complexity of the lipidome and the consequent challenges associated with analyzing it, progress in the field of lipidomics has lagged behind other omics disciplines. However, compared to the previous decade, the output of publications on lipidomics has increased more than 17-fold within the last decade and has, therefore, become one of the fastest-growing research fields. Combining multiple omics approaches will provide a unique and efficient tool for determining pathogenicity of VUS at the functional level, and thereby identifying rare, as well as novel, genetic disorders by molecular techniques and biochemical analyses.

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“…It was suggested that alterations in Fe metabolism are more pronounced in males than in females and may underlie more severe neuropsychiatric symptoms in male WD patients [268]. Systemic inflammatory response with increased plasma prostaglandins and other oxylipins was found in WD [269]. Additionally, increased serum IL-1 and TNF-alpha was observed in patients with the most severe brain MRI abnormalities [270].…”

Section: Other Genetic Disorders With Brain Iron Depositsmentioning

confidence: 99%

Cerebral Iron Deposition in Neurodegeneration

et al. 2022

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Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson’s disease, Friedreich’s disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood–brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.

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Oxylipin Profiles in Plasma of Patients with Wilson’s Disease

Cited by 13 publications

References 48 publications

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases

Cerebral Iron Deposition in Neurodegeneration

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