Lysophospholipids (LPLs) are bioactive signaling lipids that are generated from phospholipase-mediated hydrolyzation of membrane phospholipids (PLs) and sphingolipids (SLs). Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two of the best-characterized LPLs which mediate a variety of cellular physiological responses via specific G-protein coupled receptor (GPCR) mediated signaling pathways. Considerable evidence now demonstrates the crucial role of LPA and S1P in neurodegenerative diseases, especially in Alzheimer's disease (AD). Dysfunction of LPA and S1P metabolism can lead to aberrant accumulation of amyloid-β (Aβ) peptides, the formation of neurofibrillary tangles (NFTs), neuroinflammation and ultimately neuronal death. Summarizing LPA and S1P signaling profile may aid in profound health and pathological processes. In the current review, we will introduce the metabolism as well as the physiological roles of LPA and S1P in maintaining the normal functions of the nervous system. Given these pivotal functions, we will further discuss the role of dysregulation of LPA and S1P in promoting AD pathogenesis.

中文翻译：

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阿尔茨海默氏病中的溶血磷脂及其G偶联蛋白信号传导：从生理表现到病理损害。

溶血磷脂（LPL）是生物活性信号脂质，由磷脂酶介导的膜磷脂（SLs）和鞘脂（SLs）的水解产生。溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1P）是两种最典型的LPL，它们通过特定的G蛋白偶联受体（GPCR）介导的信号传导途径介导多种细胞生理反应。现在，大量证据证明了LPA和S1P在神经退行性疾病，尤其是阿尔茨海默氏病（AD）中的关键作用。LPA和S1P代谢功能异常可导致淀粉样β（Aβ）肽异常积累，神经原纤维缠结（NFT）形成，神经发炎并最终导致神经元死亡。总结LPA和S1P信号传导概况可能有助于深远的健康和病理过程。在当前的审查中，我们将介绍LPA和S1P在维持神经系统正常功能方面的代谢以及生理作用。鉴于这些关键功能，我们将进一步讨论LPA和S1P失调在促进AD发病中的作用。