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Biochemistry of very-long-chain and long-chain ceramides in cystic fibrosis and other diseases: The importance of side chain
Progress in Lipid Research ( IF 14.0 ) Pub Date : 2019-03-12 , DOI: 10.1016/j.plipres.2019.03.001
Dušan Garić , Juan B. De Sanctis , Juhi Shah , Daciana Catalina Dumut , Danuta Radzioch

Ceramides, the principal building blocks of all sphingolipids, have attracted the attention of many scientists around the world interested in developing treatments for cystic fibrosis, the most common genetic disease of Caucasians. Many years of fruitful research in this field have produced some fundamentally important, yet controversial results.

Here, we aimed to summarize the current knowledge on the role of long- and very-long- chain ceramides, the most abundant species of ceramides in animal cells, in cystic fibrosis and other diseases. We also aim to explain the importance of the length of their side chain in the context of stability of transmembrane proteins through a concise synthesis of their biophysical chemistry, cell biology, and physiology. This review also addresses several remaining riddles in this field.

Finally, we discuss the technical challenges associated with the analysis and quantification of ceramides. We provide the evaluation of the antibodies used for ceramide quantification and we demonstrate their lack of specificity. Results and discussion presented here will be of interest to anyone studying these enigmatic lipids.



中文翻译:

超长链和长链神经酰胺在囊性纤维化和其他疾病中的生物化学:侧链的重要性

神经酰胺是所有鞘脂的主要组成部分,引起了世界各地许多科学家的关注,他们对开发治疗囊性纤维化的药物感兴趣,囊性纤维化是白种人最常见的遗传疾病。在该领域多年的卓有成效的研究已经产生了一些根本上重要但有争议的结果。

在这里,我们旨在总结有关长链和超长链神经酰胺(动物细胞中最丰富的神经酰胺物种)在囊性纤维化和其他疾病中的作用的当前知识。我们还旨在通过其生物物理化学,细胞生物学和生理学的简明合成来解释跨膜蛋白稳定性背景下其侧链长度的重要性。这篇评论还解决了该领域中剩下的一些难题。

最后,我们讨论了与神经酰胺的分析和定量相关的技术挑战。我们提供了用于神经酰胺定量的抗体的评估,我们证明了它们缺乏特异性。研究这些神秘脂质的任何人都将对这里提出的结果和讨论感兴趣。

更新日期:2019-03-12
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