Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system.
The gene mutated in X-linked adrenoleukodystrophy (ALD), a progressive demyelinating disease, codes for a protein (ALDP) involved in very-long-chain fatty acid (VLCFA) transport. The expression of ALDP and of two peroxisomal enzymes involved in beta-oxidation of VLCFA, acyl-CoA oxidase, and catalase was studied in human and mouse brain. The pattern of expression was similar in both species. While acyl-CoA oxidase and catalase are found in all types of CNS cells, including neurons and oligodendrocytes, ALDP expression is restricted mostly to the white matter and endothelial cells. ALDP is highly expressed in astrocytes and microglial cells in vivo and in regenerating oligodendrocytes in vitro. In contrast, in vivo, ALDP is detected in much fewer oligodendrocytes and quantitative Western blot analysis confirmed the lower abundance of ALDP in these cells than in astrocytes. Only oligodendrocytes localized in corpus callosum, internal capsules, and anterior commissure express ALDP at levels comparable to those seen in astrocytes. In ALD, demyelination is first detected in these white matter regions, suggesting that the ALD gene mutation selectively affects those oligodendrocytes strongly expressing ALDP. Because of their failure to express ALDP, microglia and astrocytes may also contribute to demyelination in ALD patients.
Fouquet
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F
Pathologie Métabolique et Hormonale du Developpement, Hôpital St. Vincent de Paul, Paris, France.
Zhou
J M
JM
Ralston
E
E
Murray
K
K
Troalen
F
F
Magal
E
E
Robain
O
O
Dubois-Dalcq
M
M
Aubourg
P
P
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D042962:Acyl-CoA Oxidase; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002675:Child, Preschool; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008830:Microbodies / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; D010088:Oxidoreductases; D002374:Catalase; D042962:Acyl-CoA Oxidase