Semina E V, Rubina K A, Stepanova V V, Tkachuk V A
Ross Fiziol Zh Im I M Sechenova. 2016 Aug;102(8):881-903.
Recently it has been found that the urokinase receptor (uPAR) and its ligands - urokinase (uPA) and SRPX2 protein play an important role in the development and functioning of the brain. There is a strong association between uPAR gene polymorphism and autism disorders in humans. Patients with autism, intractable lobe epilepsy, verbal dyspraxia and perisylvian polymicrogyria display significant changes in uPAR expression. Mice, lacking the uPAR gene develop epilepsy and demonstrate abnormal social behavior. uPA and SRPX2 protein, have been shown to be involved in pathological brain conditions such as autism, cognitive deficits and language disorders. Urokinase system that stimulates blood vessel growth as demonstrated before, also plays an important role in the regulation of the nerve growth via matrix remodeling and activation of neurotrophic and angiogenic factors. Moreover, the urokinase system also functions as a guidance system which determines the growth trajectory of the vessels' and nerves' in tissue regeneration. This review summarizes and integrates the results and recent progress in the field of uPAR and its endogenous ligands in brain development and cognitive functions.
最近发现，尿激酶受体（uPAR）及其配体——尿激酶（uPA）和SRPX2蛋白在大脑的发育和功能中发挥着重要作用。uPAR基因多态性与人类自闭症谱系障碍之间存在密切关联。自闭症、难治性颞叶癫痫、言语失用症和外侧裂周围多小脑回患者的uPAR表达有显著变化。缺乏uPAR基因的小鼠会发生癫痫，并表现出异常的社会行为。uPA和SRPX2蛋白已被证明与自闭症、认知缺陷和语言障碍等脑部病理状况有关。如前所示，刺激血管生长的尿激酶系统在通过基质重塑以及神经营养因子和血管生成因子的激活来调节神经生长方面也发挥着重要作用。此外，尿激酶系统还作为一种引导系统，在组织再生中决定血管和神经的生长轨迹。本综述总结并整合了uPAR及其内源性配体在脑发育和认知功能领域的研究结果及最新进展。
