...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Fluids and Barriers of the CNS >The role of plasmalemma vesicle-associated protein in pathological breakdown of blood–brain and blood–retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema
【24h】

The role of plasmalemma vesicle-associated protein in pathological breakdown of blood–brain and blood–retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema

机译：质膜囊泡相关蛋白在血脑和血视网膜屏障的病理学破坏中的作用：脑水肿和糖尿病性黄斑水肿的潜在新治疗靶点

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Breakdown of the blood–brain barrier (BBB) or inner blood–retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively. However, corticosteroids have side effects, and VEGF has important neuroprotective, vascular protective and wound healing functions, implying that long-term anti-VEGF therapy may also induce adverse effects. We postulate that targeting downstream effector proteins of VEGF and other mediators that are directly involved in the regulation of BBB and BRB integrity provide more attractive and safer treatment options for vasogenic cerebral edema and diabetic macular edema. The endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans-endothelial transport, emerges as candidate for this approach. PLVAP is expressed in a subset of endothelial cells throughout the body where it forms the diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP expression in brain and eye barrier endothelia only occurs in pathological conditions associated with a compromised barrier function such as cancer, ischemic stroke and diabetic retinopathy. Here, we discuss the current understanding of PLVAP as a structural component of endothelial cells and regulator of vascular permeability in health and central nervous system disease. Besides providing a perspective on PLVAP identification, structure and function, and the regulatory processes involved, we also explore its potential as a novel therapeutic target for vasogenic cerebral edema and retinal macular edema.
机译：病理上升高的血管内皮生长因子（VEGF）或其他介体水平引起的血脑屏障（BBB）或内血视网膜屏障（BRB）分解可导致血管源性水肿和重大的临床问题，例如神经元发病和死亡率，或视力丧失。目前，脑水肿和糖尿病性黄斑水肿的主要治疗选择是通过大脑中的皮质类固醇或通过阻断眼睛中的VEGF来恢复屏障功能。但是，皮质类固醇有副作用，而VEGF具有重要的神经保护，血管保护和伤口愈合功能，这意味着长期的抗VEGF治疗也可能引起不良反应。我们假设靶向VEGF的下游效应蛋白和直接参与BBB和BRB完整性调节的其他介体为血管性脑水肿和糖尿病性黄斑水肿提供了更有吸引力和更安全的治疗选择。内皮细胞特异的血浆质膜囊泡相关蛋白（PLVAP），一种与跨内皮运输相关的蛋白，成为该方法的候选对象。 PLVAP在整个人体的内皮细胞子集中表达，在其中形成小窝，窗孔和跨内皮通道的隔膜。然而，PLVAP在脑和眼屏障内皮细胞中的表达仅在与屏障功能受损有关的病理情况下发生，例如癌症，缺血性中风和糖尿病性视网膜病。在这里，我们讨论了目前对PLVAP作为内皮细胞的结构成分和健康和中枢神经系统疾病中血管通透性调节剂的理解。除了提供有关PLVAP鉴定，结构和功能以及涉及的调控过程的观点之外，我们还探索了其作为血管源性脑水肿和视网膜黄斑水肿的新型治疗靶标的潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号