Agúndez José Ag, Jiménez-Jimenez Félix Javier, Alonso-Navarro Hortensia, García-Martín Elena
University of Extremadura, Department of Pharmacology , Avda. de la Universidad s/n, E-10071, Cáceres , Spain +34927257000 Ext 86897 ; +34924289676 ;
Expert Opin Ther Targets. 2015;19(8):1139-48. doi: 10.1517/14728222.2015.1028360. Epub 2015 Apr 10.
LINGO-1 is a negative regulator of neuronal survival, oligodendrocyte differentiation and axonal outgrowth and regeneration, because it interacts with diverse growth factor receptors blocking or inhibiting their action. Consistent findings obtained in vitro and in animal models suggest that anti-LINGO-1 therapy may be useful in neurodegenerative disorders such as multiple sclerosis (MS), Parkinson's disease or essential tremor (ET). Moreover, genetic and pathological evidence provide a robust link between LINGO-1 and ET.
In this review, we present an overview of current knowledge on findings linking LINGO-1 and ET, with a special focus on genetic linkage, we include an overview of LINGO1 gene variations according to the 1000 genomes catalog, and we identify potential gene areas where common changes occur because, as well as the risk developing ET, LINGO1 genetic changes may influence the response to anti-LINGO-1 therapy.
The goal of anti-LINGO-1 therapy in neurodegenerative diseases is to ease the brakes of neuronal growth and recovery. An anti-LINGO-1 antibody is under clinical trials for MS patients. Before planning trials with ET patients, refinement on the genetic link between LINGO1 and ET, and a detailed genetic and phenotypic assessment of ET patients to be enrolled, should be carried out.
LINGO-1是神经元存活、少突胶质细胞分化以及轴突生长和再生的负调节因子,因为它与多种生长因子受体相互作用,阻断或抑制其作用。在体外和动物模型中获得的一致研究结果表明,抗LINGO-1疗法可能对神经退行性疾病如多发性硬化症(MS)、帕金森病或特发性震颤(ET)有用。此外,遗传学和病理学证据表明LINGO-1与ET之间存在紧密联系。
在本综述中,我们概述了目前关于LINGO-1与ET之间联系的研究知识,特别关注基因连锁,我们根据千人基因组目录概述了LINGO1基因变异,并确定了常见变化发生的潜在基因区域,因为除了增加患ET的风险外,LINGO1基因变化可能会影响对抗LINGO-1疗法的反应。
神经退行性疾病中抗LINGO-1疗法的目标是缓解神经元生长和恢复的抑制因素。一种抗LINGO-1抗体正在对MS患者进行临床试验。在计划对ET患者进行试验之前,应进一步明确LINGO1与ET之间的基因联系,并对即将入组的ET患者进行详细的基因和表型评估。