The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder

Adrenoleukodystrophy (ALD) is caused by mutations in an ATP-binding-cassett e transporter located in the peroxisomal membrane, which result in a fatal demyelinating disease in boys and a milder phenotype in men and some hetero zygous women,There is no molecular signature to indicate a particular clini cal course,The underlying molecular mechanisms of this disease have yet to be targeted clinically. Is the increase in very-long-chain fatty acids (VLC FA) the disease trigger! Why is there no phenotype in ALD null mice that sh ow this increase? DoVLCFA destabilize human myelin, once formed, and lead t o the inflammation seen in this genetic disease? Bone-marrow transplantatio n might save a child by providing normal brain macrophages and allowing mye lin regeneration early in disease. The processes that underlie ALD challeng e neuroscientists to elucidate peroxisomal transporter functions in the ner vous system and to pursue the gene-transfer strategies leading to remyelina tion until a preventive therapy emerges.