Pathomechanisms Underlying X‐Adrenoleukodystrophy: A Three‐Hit Hypothesis
Open Access
- 7 June 2010
- journal article
- review article
- Published by Wiley in Brain Pathology
- Vol. 20 (4), 838-844
- https://doi.org/10.1111/j.1750-3639.2010.00392.x
Abstract
X‐adrenoleukodystrophy (X‐ALD) is a complex disease where inactivation of ABCD1 gene results in clinically diverse phenotypes, the fatal disorder of cerebral ALD (cALD) or a milder disorder of adrenomyeloneuropathy (AMN). Loss of ABCD1 function results in defective beta oxidation of very long chain fatty acids (VLCFA) resulting in excessive accumulation of VLCFA, the biochemical “hall mark” of X‐ALD. At present, the ABCD1‐mediated mechanisms that determine the different phenotype of X‐ALD are not well understood. The studies reviewed here suggest for a “three‐hit hypothesis” for neuropathology of cALD. An improved understanding of the molecular mechanisms associated with these three phases of cALD disease should facilitate the development of effective pharmacological therapeutics for X‐ALD.Keywords
This publication has 67 references indexed in Scilit:
- Very long-chain fatty acid accumulation causes lipotoxic response via 5-lipoxygenase in cerebral adrenoleukodystrophyJournal of Lipid Research, 2010
- Current and Future Pharmacological Treatment Strategies in X‐Linked AdrenoleukodystrophyBrain Pathology, 2010
- ABCD2 is abundant in adipose tissue and opposes the accumulation of dietary erucic acid (C22:1) in fatJournal of Lipid Research, 2010
- Silencing of Abcd1 and Abcd2 genes sensitizes astrocytes for inflammation: implication for X-adrenoleukodystrophyJournal of Lipid Research, 2009
- Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophagesLipids in Health and Disease, 2008
- Plasmalogen deficiency in cerebral adrenoleukodystrophy and its modulation by lovastatinJournal of Neurochemistry, 2008
- Nmnat Delays Axonal Degeneration Caused by Mitochondrial and Oxidative StressJournal of Neuroscience, 2008
- Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteineExperimental Neurology, 2008
- Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosisJCI Insight, 2008
- Oxidative Imbalance in Nonstimulated X-Adrenoleukodystrophy-Derived LymphoblastsDevelopmental Neuroscience, 2008