Isoprostanoid Plasma Levels Are Relevant to Cerebral Adrenoleukodystrophy Disease - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Life Année : 2022

Isoprostanoid Plasma Levels Are Relevant to Cerebral Adrenoleukodystrophy Disease

Résumé

Cerebral adrenoleukodystrophy (ALD) is a rare neuroinflammatory disorder characterized by progressive demyelination. Mutations within the ABCD1 gene result in very long-chain fatty acid (VLCFA) accumulation within the peroxisome, particularly in the brain. While this VLCFA accumulation is known to be the driving cause of the disease, oxidative stress can be a contributing factor. For patients with early cerebral disease, allogeneic hematopoietic stem cell transplantation (HSCT) is the standard of care, and this can be supported by antioxidants. To evaluate the involvement of fatty acid oxidation in the disease, F2-isoprostanes (F2-IsoPs), F2-dihomo-isoprostanes (F2-dihomo-IsoPs) and F4-neuroprostanes (F4-NeuroPs)—which are oxygenated metabolites of arachidonic (ARA), adrenic (AdA) and docosahexaenoic (DHA) acids, respectively—in plasma samples from ALD subjects (n = 20)—with various phenotypes of the disease-were measured. Three ALD groups were classified according to patients with: (1) confirmed diagnosis of ALD but without cerebral disease; (2) cerebral disease in early period post-HSCT (<100 days post-HSCT) and on intravenous N-acetyl-L-cysteine (NAC) treatment; (3) cerebral disease in late period post-HSCT (beyond 100 days post-HSCT) and off NAC therapy. In our observation, when compared to healthy subjects (n = 29), in ALD (i), F2-IsoPs levels were significantly (p < 0.01) increased in all patients, with the single exception of the early ALD and on NAC subjects; (ii) significant elevated (p < 0.0001) amounts of F2-dihomo-IsoPs were detected, with the exception of patients with a lack of cerebral disease; (iii), a significant increase (p < 0.003) in F4-NeuroP plasma levels was detected in all ALD patients. Moreover, F2-IsoPs plasma levels were significantly higher (p = 0.038) in early ALD in comparison to late ALD stage, and F4-NeuroPs were significantly lower (p = 0.012) in ALD subjects with a lack of cerebral disease in comparison to the late disease stage. Remarkably, plasma amounts of all investigated isoprostanoids were shown to discriminate ALD patients vs. healthy subjects. Altogether, isoprostanoids are relevant to the phenotype of X-ALD and may be helpful in predicting the presence of cerebral disease and establishing the risk of progression.
Fichier principal
Vignette du fichier
life-12-00146.pdf (3.3 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03538505 , version 1 (21-01-2022)

Licence

Paternité

Identifiants

Citer

Cinzia Signorini, Claudio de Felice, Thierry Durand, Jean-Marie Galano, Camille Oger, et al.. Isoprostanoid Plasma Levels Are Relevant to Cerebral Adrenoleukodystrophy Disease. Life, 2022, 12 (2), pp.146. ⟨10.3390/life12020146⟩. ⟨hal-03538505⟩
32 Consultations
23 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More