Changyaleket Benjarat, Deliu Zane, Chignalia Andreia Z, Feinstein Douglas L
Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA.
Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA; Jesse Brown Veteran Affairs Medical Center, Chicago, IL 60612, USA.
J Neuroimmunol. 2017 Sep 15;310:72-81. doi: 10.1016/j.jneuroim.2017.07.001. Epub 2017 Jul 5.
Heparanase is a heparan sulfate degrading enzyme that cleaves heparan sulfate (HS) chains present on HS proteoglycans (HSPGs), and has been well characterized for its roles in tumor metastasis and inflammation. However, heparanase is emerging as a contributing factor in the genesis and severity of a variety of neurodegenerative diseases and conditions. This is in part due to the wide variety of HSPGs on which the presence or absence of HS moieties dictates protein function. This includes growth factors, chemokines, cytokines, as well as components of the extracellular matrix (ECM) which in turn regulate leukocyte infiltration into the CNS. Roles for heparanase in stroke, Alzheimer's disease, and glioma growth have been described; roles for heparanase in other disease such as multiple sclerosis (MS) are less well established. However, given its known roles in inflammation and leukocyte infiltration, it is likely that heparanase also contributes to MS pathology. In this review, we will briefly summarize what is known about heparanase roles in the CNS, and speculate as to its potential role in regulating disease progression in MS and its animal model EAE (experimental autoimmune encephalitis), which may justify testing of heparanase inhibitors for MS treatment.
乙酰肝素酶是一种硫酸乙酰肝素降解酶，可切割硫酸乙酰肝素蛋白聚糖（HSPG）上的硫酸乙酰肝素（HS）链，其在肿瘤转移和炎症中的作用已得到充分表征。然而，乙酰肝素酶正逐渐成为多种神经退行性疾病及其病情发生和严重程度的一个促成因素。部分原因在于种类繁多的HSPG，其上HS部分的存在与否决定了蛋白质的功能。这包括生长因子、趋化因子、细胞因子以及细胞外基质（ECM）的成分，而细胞外基质又反过来调节白细胞向中枢神经系统的浸润。乙酰肝素酶在中风、阿尔茨海默病和胶质瘤生长中的作用已有描述；乙酰肝素酶在其他疾病如多发性硬化症（MS）中的作用尚不太明确。然而，鉴于其在炎症和白细胞浸润方面的已知作用，乙酰肝素酶很可能也与MS病理学有关。在本综述中，我们将简要总结关于乙酰肝素酶在中枢神经系统中的作用的已知情况，并推测其在调节MS及其动物模型实验性自身免疫性脑脊髓炎（EAE）疾病进展中的潜在作用，这可能为测试乙酰肝素酶抑制剂用于MS治疗提供依据。
