X-linked adrenoleukodystrophy: role of very long-chain acyl-CoA synthetases

摘要: The principal biochemical abnormality in the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD) is elevated plasma and tissue levels of very long-chain fatty acids (VLCFA). Enzymes with acyl-CoA synthetase (VLACS) activity are required for VLCFA metabolism, including degradation by peroxisomal β-oxidation or incorporation into complex lipids, may also participate synthesis. Two enzymes VLACS activity, ACSVL1 BG1, were investigated their potential role X-ALD pathology. Skin fibroblast mRNA ACSVL1, an enzyme previously shown to be peroxisomes β-oxidation, not significantly different between normal controls, patients childhood cerebral X-ALD, adrenomyeloneuropathy. Similar results obtained a non-peroxisomal that highly expressed nervous system, adrenal gland, testis, tissues pathologically affected X-ALD. No significant differences immunohistochemical staining patterns expressing either BG1 observed when wild-type mice compared. Western blot analysis protein showed no fibroblasts from adrenomyeloneuropathy patients. similar mouse brain, spinal cord, gland. We hypothesized one function was direct cholesterol ester synthesis pathway. However, depletion Neuro2a cells using RNA interference did decrease labeled esters. conclude role, if any, pathology indirect.