Open AccessPathomechanisms Underlying X‐Adrenoleukodystrophy: A Three‐Hit Hypothesis
Author(s) -
Singh Inderjit,
Pujol Aurora
Publication year - 2010
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2010.00392.x
Subject(s) - adrenoleukodystrophy , neuropathology , phenotype , disease , gene , medicine , bioinformatics , neuroscience , biology , genetics , peroxisome
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.