Lane-Donovan Courtney, Herz Joachim
Departments of Molecular Genetics and Neuroscience and Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Departments of Molecular Genetics and Neuroscience and Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390
J Lipid Res. 2017 Jun;58(6):1036-1043. doi: 10.1194/jlr.R075507. Epub 2017 Mar 14.
The LDL receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of ApoE4, an LDLR ligand, as a genetic risk factor for late-onset Alzheimer's disease has focused attention on the role this receptor family plays in the CNS. Surprisingly, it was discovered that two LDLR family members, ApoE receptor 2 (Apoer2) and VLDL receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling. This review focuses on Apoer2 and Vldlr signaling in the CNS and its role in human disease.
长期以来,人们一直在研究低密度脂蛋白受体(LDLR)家族在胆固醇运输和代谢中的作用;然而,载脂蛋白E4(ApoE4,一种LDLR配体)被确定为晚发性阿尔茨海默病的遗传风险因素后,这一受体家族在中枢神经系统(CNS)中所起的作用便受到了关注。令人惊讶的是,人们发现LDLR家族的两个成员,即载脂蛋白E受体2(Apoer2)和极低密度脂蛋白受体(Vldlr),主要通过介导Reelin信号传导,在大脑发育和成人突触可塑性中发挥关键作用。本综述聚焦于Apoer2和Vldlr在中枢神经系统中的信号传导及其在人类疾病中的作用。