Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA; Center for Translational Neurodegeneration Research, UT Southwestern Medical Center, Dallas, TX, USA.
Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA; Center for Translational Neurodegeneration Research, UT Southwestern Medical Center, Dallas, TX, USA; Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
Cell Rep. 2023 Jun 27;42(6):112669. doi: 10.1016/j.celrep.2023.112669. Epub 2023 Jun 19.
Reelin was originally identified as a regulator of neuronal migration and synaptic function, but its non-neuronal functions have received far less attention. Reelin participates in organ development and physiological functions in various tissues, but it is also dysregulated in some diseases. In the cardiovascular system, Reelin is abundant in the blood, where it contributes to platelet adhesion and coagulation, as well as vascular adhesion and permeability of leukocytes. It is a pro-inflammatory and pro-thrombotic factor with important implications for autoinflammatory and autoimmune diseases such as multiple sclerosis, Alzheimer's disease, arthritis, atherosclerosis, or cancer. Mechanistically, Reelin is a large secreted glycoprotein that binds to several membrane receptors, including ApoER2, VLDLR, integrins, and ephrins. Reelin signaling depends on the cell type but mostly involves phosphorylation of NF-κB, PI3K, AKT, or JAK/STAT. This review focuses on non-neuronal functions and the therapeutic potential of Reelin, while highlighting secretion, signaling, and functional similarities between cell types.
Reelin 最初被鉴定为神经元迁移和突触功能的调节剂，但它的非神经元功能却很少受到关注。 Reelin 参与各种组织的器官发育和生理功能，但在某些疾病中也失调。在心血管系统中，Reelin 在血液中含量丰富，有助于血小板黏附和凝血，以及白细胞黏附和血管通透性。它是一种促炎和促血栓形成的因子，对多发性硬化症、阿尔茨海默病、关节炎、动脉粥样硬化或癌症等自身免疫和自身免疫性疾病有重要影响。从机制上讲，Reelin 是一种大型分泌糖蛋白，可与几种膜受体结合，包括 ApoER2、VLDLR、整合素和 ephrins。 Reelin 信号取决于细胞类型，但主要涉及 NF-κB、PI3K、AKT 或 JAK/STAT 的磷酸化。这篇综述重点介绍了 Reelin 的非神经元功能和治疗潜力，同时强调了细胞类型之间分泌、信号和功能的相似性。
