Cerebral inflammation in X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disease that affects approximately 1 in 25 000 males. It is characterized by elevated levels of saturated very long chain fatty acids (VLCFA), i.e., >C22:0, particularly in ganglioside and cholesterol ester fractions of brain white matter and adrenal cortex. Failure of peroxisomal very long chain fatty acyl-CoA synthetase (VLCS) to activate these VLCFA prevents their degradation by peroxisomal beta-oxidation. X-ALD maps to Xq28 and the gene encodes a peroxisomal membrane protein and not the gene for VLCS. The two most common forms of X-ALD are the cerebral (CER) form, with an inflammatory demyelinating reaction that resembles multiple sclerosis (MS), and adrenomyeloneuropathy (AMN), which involves the spinal cord and in which the inflammatory reaction is mild or absent. Investigations into the nature of the cerebral inflammatory demyelinating reaction in X-ALD will be the subject of this review.
McGuinness
M C
MC
Department of Neurology, Johns Hopkins University School of Medicine, and The Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
Smith
K D
KD
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000326:Adrenoleukodystrophy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017668:Age of Onset; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002648:Child; D016207:Cytokines / Q000502:physiology; D003711:Demyelinating Diseases / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005227:Fatty Acids / Q000378:metabolism; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020675:Peroxisomes / Q000737:chemistry / Q000201:enzymology; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology; D014960:X Chromosome
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D016207:Cytokines; D005227:Fatty Acids; D006680:HLA Antigens; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha