Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients

Fujiwara, Yuko; Hama, Kotaro; Shimozawa, Nobuyuki; Yokoyama, Kazuaki

doi:10.3390/ijms22168645

Cited by 8 publications

(2 citation statements)

References 40 publications

(42 reference statements)

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“…Diagnosis of brain injury by magnetic resonance imaging (MRI) or clinical symptoms is extremely limited because most patients are already in an advanced stage of the disease; in some cases, inflammatory demyelination was found after autopsy. Some studies have used skin fibroblasts to predict disease severity by measuring levels of glycosphingolipid (GSL) species, reflecting more complex lipid metabolism (61). Researchers have even taken skin biopsies to extract and cultureinduced pluripotent stem cells (iPSCs) to mimic brain tissue to get an early and accurate diagnosis of X-ALD (62).…”

Section: Redox Imbalance and Inflammatory Markers In The Blood Reflec...mentioning

confidence: 99%

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

Chen

Guo

et al. 2022

Front. Nutr.

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X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). The pathophysiological mechanisms of ALD remain unclear, but some in vitro/in vivo research showed that VLCFA could induce oxidative stress and inflammation, leading to damage. In addition, the evidence that oxidative stress and inflammation are increased in patients with X-ALD also proves that it is a potential mechanism of brain and adrenal damage. Therefore, normalizing the redox balance becomes a critical therapeutic target. This study focuses on the possible predictors of the severity and progression of X-ALD, the potential mechanisms of pathogenesis, and the promising targeted drugs involved in oxidative stress and inflammation.

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Section: Redox Imbalance and Inflammatory Markers In The Blood Reflec...mentioning

confidence: 99%

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

Chen

Guo

et al. 2022

Front. Nutr.

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“…However, the limited number of samples and the inclusion of up to seven biological replicates for each cell line hinders the interpretation of these findings. Fujiwara et al performed a lipidomics analysis with a focus on glycosphingolipids on fibroblasts from four childhood cerebral ALD patients, three myelopathy patients, and five healthy controls [ 49 ]. Several VLCFA-containing glycosphingolipid and sphingomyelin species were elevated in fibroblasts from ALD patients compared to controls.…”

Section: Biomarker Studies So Farmentioning

confidence: 99%

Molecular Biomarkers for Adrenoleukodystrophy: An Unmet Need

Honey

Jaspers

Engelen

et al. 2021

Cells

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X-linked adrenoleukodystrophy (ALD) is an inherited progressive neurometabolic disease caused by mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids in plasma and tissues. Patients present with heterogeneous clinical manifestations which can include adrenal insufficiency, myelopathy, and/or cerebral demyelination. In the absence of a genotype-phenotype correlation, the clinical outcome of an individual cannot be predicted and currently there are no molecular markers available to quantify disease severity. Therefore, there is an unmet clinical need for sensitive biomarkers to monitor and/or predict disease progression and evaluate therapy efficacy. The increasing amount of biological sample repositories (‘biobanking’) as well as the introduction of newborn screening creates a unique opportunity for identification and evaluation of new or existing biomarkers. Here we summarize and review the many studies that have been performed to identify and improve knowledge surrounding candidate molecular biomarkers for ALD. We also highlight several shortcomings of ALD biomarker studies, which often include a limited sample size, no collection of longitudinal data, and no validation of findings in an external cohort. Nonetheless, these studies have generated a list of interesting biomarker candidates and this review aspires to direct future biomarker research.

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