Increased ceramide in brains with Alzheimer's and other neurodegenerative diseases.
Increased ceramide in brains with Alzheimer's and other neurodegenerative diseases.
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DOI：
10.3233/jad-2011-111202
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Duerksen-Hughes PJ
中科院分区：
文献类型：
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作者：
Filippov V;Song MA;Zhang K;Vinters HV;Tung S;Kirsch WM;Yang J;Duerksen-Hughes PJ
神经酰胺已被认为参与导致阿尔茨海默病（AD）的神经元细胞死亡，但其作用尚不清楚。我们比较了患有阿尔茨海默病、其他神经病理疾病或两者兼有的患者大脑中6种神经酰胺亚种的水平，它们的脂肪酸部分长度不同。我们发现，在任何被测试的神经缺陷患者的大脑中，Cer16、Cer18、Cer20和Cer24的水平都有所升高。此外，神经酰胺水平在有一种以上神经病理异常的患者中最高。有趣的是，在有神经缺陷的大脑中，该数值范围比对照组高，这表明神经酰胺合成的调节通常受到严格控制，而这种严格控制可能在神经退行性变期间失去。然而，这些变化并没有改变被测神经酰胺种类之间的比例。为了探索这种失调的机制，我们评估了与神经酰胺代谢相关的四个基因的表达：ASMase、NSMase 2、GALC和UGCG。基因表达模式很复杂，但总体而言，与年龄匹配的对照组相比，来自神经病理异常患者的标本中ASMase、NSMase 2和GALC表达上调。这些发现表明，这些基因在诊断和干预神经退行性过程方面都是有吸引力的候选者。
Ceramide has been suggested to participate in the neuronal cell death that leads to Alzheimer’s disease (AD), but its role is not yet well-understood. We compared the levels of six ceramide subspecies, which differ in the length of their fatty acid moieties, in brains from patients who suffered from AD, other neuropathological disorders, or both. We found elevated levels of Cer16, Cer18, Cer20, and Cer24 in brains from patients with any of the tested neural defects. Moreover, ceramide levels were highest in patients with more than one neuropathologic abnormality. Interestingly, the range of values was higher among brains with neural defects than in controls, suggesting that the regulation of ceramide synthesis is normally under tight control, and that this tight control may be lost during neurodegeneration. These changes, however, did not alter the ratio between the tested ceramide species. To explore the mechanisms underlying this dysregulation, we evaluated the expression of four genes connected to ceramide metabolism: ASMase, NSMase 2, GALC, and UGCG. The patterns of gene expression were complex, but overall, ASMase, NSMase 2, and GALC were upregulated in specimens from patients with neuropathologic abnormalities in comparison with age-matched controls. Such findings suggest these genes as attractive candidates both for diagnostic purposes and for intervening in neurodegenerative processes.