Gonzalo-Gobernado Rafael, Calatrava-Ferreras Lucia, Perucho Juan, Reimers Diana, Casarejos MarIa J, Herranz Antonio S, Jimenez-Escrig Adriano, Diaz-Gil Juan J, Bazan Eulalia
Servicio de Neurobiologia- Investigacion, Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS). Madrid, 28034, Spain.
Recent Pat CNS Drug Discov. 2014;9(3):173-80. doi: 10.2174/1574889809666141224123303.
Liver growth factor (LGF) is a hepatic mitogen purified by our group in 1986. In the following years we demonstrated its activity both in "in vivo" and "in vitro" systems, stimulating hepatocytes mitogenesis as well as liver regeneration in several models of liver injury. Furthermore, we established its chemical composition (albumin-bilirubin complex) and its mitogenic actions in liver. From 2000 onwards we used LGF as a tissue regenerating factor in several models of extrahepatic diseases. The use of Liver growth factor as a neural tissue regenerator has been recently protected (Patent No US 2014/8,642,551 B2). LGF administration stimulates neurogenesis and neuron survival, promotes migration of newly generated neurons, and induces the outgrowth of striatal dopaminergic terminals in 6-hidroxydopamine-lesioned rats. Furthermore, LGF treatment raises striatal dopamine levels and protects dopaminergic neurons in hemiparkinsonian animals. LGF also stimulates survival of grafted foetal neural stem cells in the damaged striatum, reduces rotational behaviour and improves motor coordination. Interestingly, LGF also exerts a neuroprotective role both in an experimental model of cerebellar ataxia and in a model of Friedrich´s ataxia. Microglia seem to be the cellular target of LGF in the CNS. Moreover, the activity of the factor could be mediated by the stimulation of MAPK´s signalling pathway and by regulating critical proteins for cell survival, such as Bcl-2 and phospho-CREB. Since the factor shows neuroprotective and neurorestorative effects we propose LGF as a patented novel therapeutic tool that may be useful for the treatment of Parkinson´s disease and cerebellar ataxias. Currently, our studies have been extended to other neurological disorders such as Alzheimer's disease (Patent No: US 2014/0113859 A1).
肝脏生长因子(LGF)是我们团队于1986年纯化出的一种肝脏有丝分裂原。在随后的几年里,我们在“体内”和“体外”系统中证实了其活性,在多种肝损伤模型中刺激肝细胞有丝分裂以及肝脏再生。此外,我们确定了其化学组成(白蛋白 - 胆红素复合物)及其在肝脏中的促有丝分裂作用。从2000年起,我们在多种肝外疾病模型中使用LGF作为组织再生因子。肝脏生长因子作为神经组织再生剂的用途最近已获得专利保护(美国专利号2014/8,642,551 B2)。给予LGF可刺激神经发生和神经元存活,促进新生成神经元的迁移,并在6 - 羟基多巴胺损伤的大鼠中诱导纹状体多巴胺能终末的生长。此外,LGF治疗可提高纹状体多巴胺水平,并保护偏侧帕金森病动物中的多巴胺能神经元。LGF还可刺激受损纹状体中移植的胎儿神经干细胞的存活,减少旋转行为并改善运动协调性。有趣的是,LGF在小脑共济失调的实验模型和弗里德里希共济失调模型中也发挥神经保护作用。小胶质细胞似乎是中枢神经系统中LGF的细胞靶点。此外,该因子的活性可能通过刺激MAPK信号通路以及调节细胞存活的关键蛋白(如Bcl - 2和磷酸化CREB)来介导。由于该因子具有神经保护和神经修复作用,我们提出将LGF作为一种获得专利的新型治疗工具,可能对帕金森病和小脑共济失调的治疗有用。目前,我们的研究已扩展到其他神经系统疾病,如阿尔茨海默病(专利号:美国2014/0113859 A1)。