Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Int J Mol Sci. 2018 Jun 21;19(7):1827. doi: 10.3390/ijms19071827.
The brain contains various forms of lipids that are important for maintaining its structural integrity and regulating various signaling cascades. Autotaxin (ATX) is an ecto-nucleotide pyrophosphatase/phosphodiesterase-2 enzyme that hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid (LPA). LPA is a major bioactive lipid which acts through G protein-coupled receptors (GPCRs) and plays an important role in mediating cellular signaling processes. The majority of synthesized LPA is derived from membrane phospholipids through the action of the secreted enzyme ATX. Both ATX and LPA are highly expressed in the central nervous system. Dysfunctional expression and activity of ATX with associated changes in LPA signaling have recently been implicated in the pathogenesis of Alzheimer's disease (AD). This review focuses on the current understanding of LPA signaling, with emphasis on the importance of the autotaxin⁻lysophosphatidic acid (ATX⁻LPA) pathway and its alterations in AD and a brief note on future therapeutic applications based on ATX⁻LPA signaling.
大脑中含有多种形式的脂质，这些脂质对于维持其结构完整性和调节各种信号级联反应非常重要。自分泌酶（ATX）是一种胞外核苷酸磷酸二酯酶-2 酶，可将细胞外溶血磷脂水解为脂质介质溶血磷脂酸（LPA）。LPA 是一种主要的生物活性脂质，通过 G 蛋白偶联受体（GPCR）发挥作用，在调节细胞信号转导过程中发挥重要作用。大多数合成的 LPA 是通过分泌酶 ATX 的作用从膜磷脂衍生而来的。ATX 和 LPA 在中枢神经系统中均高度表达。ATX 的功能失调表达和活性以及与 LPA 信号转导相关的变化最近被牵连到阿尔茨海默病（AD）的发病机制中。本综述重点介绍了 LPA 信号转导的最新认识，强调了自分泌酶⁻溶血磷脂酸（ATX⁻LPA）途径的重要性及其在 AD 中的改变，并简要介绍了基于 ATX⁻LPA 信号转导的未来治疗应用。
