Pathomechanisms Underlying X-Adrenoleukodystrophy: A Three-Hit Hypothesis
Version of Record online: 7 JUN 2010
© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology
Volume 20, Issue 4, pages 838–844, July 2010
How to Cite
Singh, I. and Pujol, A. (2010), Pathomechanisms Underlying X-Adrenoleukodystrophy: A Three-Hit Hypothesis. Brain Pathology, 20: 838–844. doi: 10.1111/j.1750-3639.2010.00392.x
- Issue online: 7 JUN 2010
- Version of Record online: 7 JUN 2010
- Received 5 March 2010; accepted 8 March 2010.
- axonal degeneration;
- oxidative stress;
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.