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神经血管联系:从遗传学见解到治疗前景

Neuro-vascular link: from genetic insights to therapeutic perspectives.

作者信息

Carmeliet P

机构信息

Vesalius Research Center, Department of Molecular and Cellular Medicine, K.U.Leuven.

出版信息

Bull Mem Acad R Med Belg. 2008;163(10-12):445-51; discussion 451-2.

Abstract

Understanding the molecular basis of the formation of blood vessels (angiogenesis) and nerves (neurogenesis) is of great medical relevance. It is well known that dysregulation of angiogenesis leads to tissue ischemia, cancer, inflammation and other disorders, while a dysfunction of the nerve system contributes to motorneuron disorders like amyotrophic lateral sclerosis (ALs) and other neurodegenerative diseases. The observations of Andreas Vesalius--Belgian anatomist of the 16th century--that patterning ofvessels and nerves show more than remarkable similarities, are currently revisited in exciting studies. Indeed, often, vessels and nerves even track alongside each other. Recent genetic studies revealed that vessels and nerves share many more common principles and signals for navigation, proliferation and survival than previously suspected. For instance, gene inactivation studies in mice and zebrafish showed that axon guidance signals regulate vessel navigation. Conversely, prototypic angiogenic factors such as VEGF control neurogenesis and regulate axon and neuron guidance, independently of their angiogenic activity. The next coming years promise to become an exciting journey to further unravel the molecular basis and explore the therapeutic potential of the neurovascular link.

摘要

了解血管生成(angiogenesis)和神经发生(neurogenesis)形成的分子基础具有重大的医学意义。众所周知,血管生成失调会导致组织缺血、癌症、炎症及其他疾病,而神经系统功能障碍则会引发运动神经元疾病,如肌萎缩侧索硬化症(ALS)和其他神经退行性疾病。16世纪比利时解剖学家安德烈亚斯·维萨里(Andreas Vesalius)观察到血管和神经的形成模式存在惊人的相似之处,目前在令人兴奋的研究中得以重新审视。事实上,血管和神经常常相互伴行。最近的遗传学研究表明,血管和神经在导航、增殖和存活方面共享的共同原理和信号比之前认为的更多。例如,对小鼠和斑马鱼的基因失活研究表明,轴突导向信号可调节血管导航。相反,诸如血管内皮生长因子(VEGF)等典型的血管生成因子可控制神经发生,并调节轴突和神经元导向,这与其血管生成活性无关。未来几年有望成为一段令人兴奋的旅程,进一步揭示分子基础并探索神经血管联系的治疗潜力。

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