期刊
BIOCHIMIE
卷 98, 期 -, 页码 143-149出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2013.09.012
关键词
X-linked adrenoleukodystrophy; Oxidative damage; Mitochondria dysfunction; Very long-chain fatty acids; Cyclophilin D; Proteasome
资金
- European Commission [FP7-241622]
- European Leukodystrophy Association [ELA2009-035I4, ELA2009-036C5, ELA2008-040C4]
- Spanish Institute for Health Carlos III [FIS PI080991, FIS PI11/01043, CP11/00080]
- Oliver's army
- Hesperia Foundation
- Autonomous Government of Catalonia [2009SGR85]
- ICREA Funding Source: Custom
X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease (minimal incidence 1:17,000). It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of VLCFA (very long-chain fatty acids) in organs and plasma. Understanding of the aetiopathogenesis is a prerequisite for the development of novel therapeutic strategies. Functional genomics analysis of an ABCD1 null mouse, a mouse model for adrenomyeloneuropathy, has revealed presymptomatic alterations in several metabolic pathways converging on redox and bioenergetic homeostasis, with failure of mitochondrial OXPHOS disruption and mitochondrial depletion. These defects could be major contributors to the neurodegenerative cascade, as has been reported in several neurodegenerative disorders. Drugs targeting the redox imbalance/mitochondria dysfunction interplay have shown efficacy at halting axonal degeneration and associated disability in the mouse, and thus offer therapeutic hope. (C) 2013 Elsevier Masson SAS. All rights reserved.
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