骨桥蛋白在神经退行性疾病中的作用

The Role of Osteopontin in Neurodegenerative Diseases

骨桥蛋白(OPN)是一种分子量约为60 KDa的糖基化磷蛋白,广泛分布于骨、脑、肾、肺以及肝等多种重要的脏器组织中。该蛋白通过与整合素、CD44V等受体结合,参与应激反应,癌症,骨重建,炎性反应以及感染等多种生理病理性进展。由于早期分泌OPN能够诱发细胞的激活,故OPN也被称为ETA-1(早期T淋巴细胞激活因子-1)。目前发现,OPN存在两种形式:一种是分泌型骨桥蛋白(sOPN),另一种是胞内型骨桥蛋白(iOPN)。在体内,二者通过不同的作用途径参与免疫调节过程。近年来,随着分子生物学的进展以及对神经退行性疾病研究的不断深入,发现OPN在神经退行性疾病中似乎发挥着双刃剑的作用,即在某些特定情况下,它能够激发神经毒性和神经元的死亡;而在其他情况下,它起到的是神经保护性作用。本文就OPN的结构特点、生物学功能以及在神经退行性病变中的作用进行简要归纳。

Osteopontin（OPN） is a 60 KDa glycosylated phosphoprotein,distributed in a variety of tissues such as bone,brain,kidney,lung and liver.Combined with integrins or CD44v,OPN involves in various of functions in pathophysiologic processes including stress response,cancer,bone,remodeling,inflammation and neurodegeneration.Because of its early production upon cell activation,OPN is also called ETA-1（early T-cell activation-1）.Recently,it makes clear that there are two isoforms of OPN,one is a secreted form of Opn（s-Opn） and the other one is an intracellular form of Opn（i-OPN）,both involved in immune regulation process through different pathways.With the rapid development of molecular biology and progress of OPN research,it is found that OPN seems to act as a double-edged sword in neurodegenerative diseases by triggering neuronal toxicity and death under certain circumstances and functioning as a neuroprotectant under others.This review will provide an overview of the state of the art of what is currently known about the characteristic structure and biological function of OPN and the role of it in the neurodegenerative diseases.