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首页> 外文期刊>The European Journal of Neuroscience >Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain.
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Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain.

机译:阿尔茨海默氏病脑中酸性神经酰胺酶水平和活性的升高。

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摘要

Abstract Protein glycosylation modifies the processing of several key proteins involved in the molecular pathogenesis of Alzheimer's disease (AD). Aberrant glycosylation of tau and down-regulation of sialyltransferase in AD brain suggest a possible dysregulation of protein glycosylation that may play a role in AD. We therefore isolated major glycoproteins from AD brain by using lectin-affinity chromatographies and ion-exchange chromatography and further separated them using SDS-polyacylamide gel electrophoresis. Mass spectrometry analysis of 11 isolated glycoproteins led to their identification as: neuronal cell adhesion molecule, beta-globin, IgM heavy chain VH1 region precursor, contactin precursor, dipeptidylpeptidase VI, CD81 partner 3, prenylcysteine lyase, adipocyte plasma-associated protein, acid ceramidase and two novel proteins. We found that the level and activity of acid ceramidase (AC), one of the major identified human brain glycoproteins, were significantly elevated in AD brain. Immunohistochemical staining indicated that AC was located mainly in the cell bodies of neurons and colocalized with neurofibrillary tangles. Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC-mediated signalling pathways might be involved in the molecular mechanism of AD.
机译:摘要蛋白质糖基化修饰了与阿尔茨海默氏病(AD)分子发病机理有关的几种关键蛋白质的加工过程。 tau的异常糖基化和AD脑中唾液酸转移酶的下调提示可能在AD中起作用的蛋白质糖基化可能失调。因此,我们使用凝集素亲和层析和离子交换层析从AD脑中分离出主要糖蛋白,并使用SDS-聚丙烯酰胺凝胶电泳进一步分离它们。质谱分析了11种分离的糖蛋白,结果鉴定为:神经元细胞粘附分子,β-球蛋白,IgM重链VH1区前体,接触素前体,二肽基肽酶VI,CD81伴侣3,异戊二烯半胱氨酸裂解酶,脂肪细胞血浆相关蛋白,酸性神经酰胺酶和两种新型蛋白质。我们发现酸性神经酰胺酶(AC)的水平和活性,主要鉴定的人脑糖蛋白之一,在AD脑中显着升高。免疫组织化学染色表明AC主要位于神经元的细胞体中,并与神经原纤维缠结共定位。我们的发现表明AC可能在控制神经元凋亡中起作用,并且AC介导的信号通路可能与AD的分子机制有关。

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