Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE-CONICET), X5016DHK Córdoba, Argentina.
Int J Mol Sci. 2019 Jul 21;20(14):3564. doi: 10.3390/ijms20143564.
Sphingolipids (SL) modulate several cellular processes including cell death, proliferation and autophagy. The conversion of sphingomyelin (SM) to ceramide and the balance between ceramide and sphingosine-1-phosphate (S1P), also known as the SL rheostat, have been associated with oxidative stress and neurodegeneration. Research in the last decade has focused on the possibility of targeting the SL metabolism as a therapeutic option; and SL levels in biofluids, including serum, plasma, and cerebrospinal fluid (CSF), have been measured in several neurodegenerative diseases with the aim of finding a diagnostic or prognostic marker. Previous reviews focused on results from diseases such as Alzheimer's Disease (AD), evaluated total SL or species levels in human biofluids, post-mortem tissues and/or animal models. However, a comprehensive review of SL alterations comparing results from several neurodegenerative diseases is lacking. The present work compiles data from circulating sphingolipidomic studies and attempts to elucidate a possible connection between certain SL species and neurodegeneration processes. Furthermore, the effects of ceramide species according to their acyl-chain length in cellular pathways such as apoptosis and proliferation are discussed in order to understand the impact of the level alteration in specific species. Finally, enzymatic regulations and the possible influence of insulin resistance in the level alteration of SL are evaluated.
鞘脂类（SL）调节包括细胞死亡、增殖和自噬在内的多种细胞过程。鞘磷脂（SM）向神经酰胺的转化以及神经酰胺和鞘氨醇-1-磷酸（S1P）之间的平衡，也称为 SL 变阻器，与氧化应激和神经退行性变有关。过去十年的研究集中在将 SL 代谢作为一种治疗选择作为目标的可能性上；并且在几种神经退行性疾病中测量了生物流体（包括血清、血浆和脑脊液（CSF）中的 SL 水平，旨在寻找诊断或预后标志物。以前的综述重点关注阿尔茨海默病（AD）等疾病的结果，评估了人类生物流体、尸检组织和/或动物模型中的总 SL 或物种水平。然而，缺乏对几种神经退行性疾病的 SL 改变进行综合比较的综述。本工作汇集了循环鞘脂组学研究的数据，并试图阐明某些 SL 物种与神经退行性变过程之间的可能联系。此外，根据其酰基链长度讨论了神经酰胺物种在细胞途径（如细胞凋亡和增殖）中的作用，以了解特定物种水平改变的影响。最后，评估了酶调节以及胰岛素抵抗对 SL 水平改变的可能影响。
