Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.
Int J Mol Sci. 2023 Mar 24;24(7):6180. doi: 10.3390/ijms24076180.
Sphingosine-1-phosphate lyase (SPL) is a pyridoxal 5'-phosphate-dependent enzyme involved in the irreversible degradation of sphingosine-1-phosphate (S1P)-a bioactive sphingolipid that modulates a broad range of biological processes (cell proliferation, migration, differentiation and survival; mitochondrial functioning; and gene expression). Although SPL activity leads to a decrease in the available pool of S1P in the cell, at the same time, hexadecenal and phosphoethanolamine, compounds with potential biological activity, are generated. The increased expression and/or activity of SPL, and hence the imbalance between S1P and the end products of its cleavage, were demonstrated in several pathological states. On the other hand, loss-of-function mutations in the SPL encoding gene are a cause of severe developmental impairments. Recently, special attention has been paid to neurodegenerative diseases as the most common pathologies of the nervous system. This review summarizes the current findings concerning the role of SPL in the nervous system with an emphasis on neurodegeneration. Moreover, it briefly discusses pharmacological compounds directed to inhibit its activity.
鞘氨醇-1-磷酸裂解酶（SPL）是一种依赖于吡哆醛 5'-磷酸的酶，参与鞘氨醇-1-磷酸（S1P）的不可逆降解，S1P 是一种生物活性鞘脂，调节广泛的生物过程（细胞增殖、迁移、分化和存活；线粒体功能；和基因表达）。尽管 SPL 活性导致细胞中 S1P 的可用池减少，但同时也生成了具有潜在生物学活性的十六烯醛和磷酸乙醇胺化合物。在几种病理状态下，已经证明 SPL 的表达和/或活性增加，以及 S1P 和其裂解产物之间的不平衡。另一方面，SPL 编码基因的功能丧失突变是严重发育障碍的原因。最近，人们特别关注神经系统的退行性疾病作为最常见的神经病理学。本综述总结了 SPL 在神经系统中的作用的最新发现，重点是神经退行性变。此外，还简要讨论了针对抑制其活性的药理学化合物。
