Over the past decade, it was found that relatively simple sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate, and glucosylceramide play important roles in neuronal functions by regulating rates of neuronal growth and differentiation. Homeostasis of membrane sphingolipids in neurons and myelin is essential to prevent the loss of synaptic plasticity, cell death and neurodegeneration. In our review we summarize data about significant brain cell alterations of sphingolipids in different neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, Amyotrophic Lateral Sclerosis, Gaucher's, Farber's diseases, etc. We reported results obtained in brain tissue from both animals in which diseases were induced and humans in autopsy samples. Moreover, attention was paid on sphingolipids in biofluids, liquor and blood, from patients. In Alzheimer's disease sphingolipids are involved in the processing and aggregation of β-amyloid and in the transmission of the cytotoxic signal β-amyloid and TNFα-induced. Recently, the gangliosides metabolism in transgenic animals and the relationship between blood sphingolipids changes and cognitive impairment in Alzheimer's disease patients have been intensively studied. Numerous experiments have highlighted the involvement of ceramide and monohexosylceramide metabolism in the pathophysiology of the sporadic forms of Parkinson's disease. Moreover, gene mutations of the glucocerebrosidase enzyme were considered as responsible for Parkinson's disease via transition of the monomeric form of α-synuclein to an oligomeric, aggregated toxic form. Disturbances in the metabolism of ceramides were also associated with the appearance of Lewy's bodies. Changes in sphingolipid metabolism were found as a manifestation of Amyotrophic Lateral Sclerosis, both sporadic and family forms, and affected the rate of disease development. Currently, fingolimod (FTY720), a sphingosine-1-phosphate receptor modulator, is the only drug undergoing clinical trials of phase II safety for the treatment of Amyotrophic Lateral Sclerosis. The use of sphingolipids as new diagnostic markers and as targets for innovative therapeutic strategies in different neurodegenerative disorders has been included.

中文翻译：

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探索鞘脂对神经退行性变的影响。


在过去的十年中，人们发现相对简单的鞘脂，如神经酰胺、鞘氨醇、1-磷酸鞘氨醇和葡萄糖神经酰胺通过调节神经元生长和分化速率在神经元功能中发挥重要作用。神经元和髓磷脂中膜鞘脂的稳态对于防止突触可塑性丧失、细胞死亡和神经变性至关重要。在我们的综述中，我们总结了不同神经退行性疾病（如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、戈谢病、法伯病等）中鞘脂类脑细胞显着改变的数据。我们报告了从患有该病的两种动物的脑组织中获得的结果诱导和尸检样本中的人类。此外，患者的生物体液、液体和血液中的鞘脂也受到关注。在阿尔茨海默病中，鞘脂参与β-淀粉样蛋白的加工和聚集，以及β-淀粉样蛋白和TNFα诱导的细胞毒性信号的传递。近年来，转基因动物神经节苷脂代谢以及阿尔茨海默病患者血液鞘脂变化与认知障碍的关系得到深入研究。许多实验强调了神经酰胺和单己糖神经酰胺代谢在散发性帕金森病的病理生理学中的参与。此外，葡萄糖脑苷脂酶的基因突变被认为是通过α-突触核蛋白单体形式转变为寡聚、聚集毒性形式而导致帕金森病的原因。神经酰胺代谢紊乱也与路易体的出现有关。 鞘脂代谢的变化被发现是肌萎缩侧索硬化症的一种表现，无论是散发性还是家族性形式，都会影响疾病的发展速度。目前，1-磷酸鞘氨醇受体调节剂芬戈莫德（FTY720）是唯一正在进行治疗肌萎缩侧索硬化症II期安全性临床试验的药物。其中包括使用鞘脂作为新的诊断标记物和作为不同神经退行性疾病创新治疗策略的靶标。