Lütjohann Dieter, Harzer Klaus, Gieselmann Volkmar, Eckhardt Matthias
Institute of Clinical Pharmacology, University of Bonn, Germany.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):647-50. doi: 10.1016/j.bbrc.2006.03.186. Epub 2006 Apr 7.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by deficiency in arylsulfatase A (ASA). Concentrations of cholesterol and its metabolites were determined in ASA deficient [ASA(-/-)] mice which serve as an animal model of MLD. We observed a significant reduction in cholesterol content in the brain of adult ASA(-/-) mice when compared to wild-type controls. This was not due to loss of myelin, because ASA(-/-) mice do not demyelinate. Other cholesterol metabolites were not changed significantly in ASA(-/-) mice, except for an increase in lathosterol. Moreover, reduced cholesterol levels were also found in tissue samples from two juvenile MLD cases. Since high cholesterol levels are important for myelination, and various cellular processes, like vesicular trafficking and signal transduction, reduced cholesterol levels might be an important factor in the molecular pathology of MLD.
异染性脑白质营养不良（MLD）是一种由芳基硫酸酯酶A（ASA）缺乏引起的溶酶体贮积症。在作为MLD动物模型的ASA缺陷型[ASA(-/-)]小鼠中测定了胆固醇及其代谢物的浓度。与野生型对照相比，我们观察到成年ASA(-/-)小鼠大脑中的胆固醇含量显著降低。这并非由于髓鞘丢失，因为ASA(-/-)小鼠不会发生脱髓鞘。除了羊毛甾醇增加外，ASA(-/-)小鼠中的其他胆固醇代谢物没有显著变化。此外，在两例青少年MLD病例的组织样本中也发现胆固醇水平降低。由于高胆固醇水平对髓鞘形成以及各种细胞过程（如囊泡运输和信号转导）很重要，胆固醇水平降低可能是MLD分子病理学中的一个重要因素。
