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The noncanonical chronicles: Emerging roles of sphingolipid structural variants
Cellular Signalling ( IF 4.8 ) Pub Date : 2020-12-28 , DOI: 10.1016/j.cellsig.2020.109890
Brenda Wan Shing Lam 1 , Ting Yu Amelia Yam 1 , Christopher P Chen 2 , Mitchell K P Lai 2 , Wei-Yi Ong 3 , Deron R Herr 4
Affiliation  

Sphingolipids (SPs) are structurally diverse and represent one of the most quantitatively abundant classes of lipids in mammalian cells. In addition to their structural roles, many SP species are known to be bioactive mediators of essential cellular processes. Historically, studies have focused on SP species that contain the canonical 18‑carbon, mono-unsaturated sphingoid backbone. However, increasingly sensitive analytical technologies, driven by advances in mass spectrometry, have facilitated the identification of previously under-appreciated, molecularly distinct SP species. Many of these less abundant species contain noncanonical backbones. Interestingly, a growing number of studies have identified clinical associations between these noncanonical SPs and disease, suggesting that there is functional significance to the alteration of SP backbone structure. For example, associations have been found between SP chain length and cardiovascular disease, pain, diabetes, and dementia. This review will provide an overview of the processes that are known to regulate noncanonical SP accumulation, describe the clinical correlations reported for these molecules, and review the experimental evidence for the potential functional implications of their dysregulation. It is likely that further scrutiny of noncanonical SPs may provide new insight into pathophysiological processes, serve as useful biomarkers for disease, and lead to the design of novel therapeutic strategies.



中文翻译:

非经典编年史:鞘脂结构变异的新兴作用

鞘脂 (SPs) 结构多样,是哺乳动物细胞中数量最多的一类脂质。除了它们的结构作用外,已知许多 SP 物种是基本细胞过程的生物活性介质。从历史上看,研究主要集中在含有典型 18 碳单不饱和鞘氨醇骨架的 SP 物种上。然而,在质谱技术进步的推动下,越来越敏感的分析技术促进了以前被低估的、分子上不同的 SP 物种的鉴定。许多这些不太丰富的物种包含非规范的主链。有趣的是,越来越多的研究已经确定了这些非典型 SP 与疾病之间的临床关联,表明SP骨架结构的改变具有功能意义。例如,已经发现 SP 链长度与心血管疾病、疼痛、糖尿病和痴呆之间存在关联。这篇综述将概述已知的调节非典型 SP 积累的过程,描述这些分子的临床相关性,并回顾实验证据,了解它们失调的潜在功能影响。对非经典 SP 的进一步审查可能会为病理生理过程提供新的见解,作为疾病的有用生物标志物,并导致设计新的治疗策略。这篇综述将概述已知的调节非典型 SP 积累的过程,描述这些分子的临床相关性,并回顾实验证据,了解它们失调的潜在功能影响。对非经典 SP 的进一步审查可能会为病理生理过程提供新的见解,作为疾病的有用生物标志物,并导致设计新的治疗策略。这篇综述将概述已知的调节非典型 SP 积累的过程,描述这些分子的临床相关性,并回顾实验证据,了解它们失调的潜在功能影响。对非经典 SP 的进一步审查可能会为病理生理过程提供新的见解,作为疾病的有用生物标志物,并导致设计新的治疗策略。

更新日期:2020-12-29
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