Siehr Meagan S, Noebels Jeffrey L
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Curr Opin Neurobiol. 2016 Feb;36:82-8. doi: 10.1016/j.conb.2015.10.007. Epub 2015 Oct 27.
The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several genes, even those linked to malformations, show promise for postnatal correction before the onset of their clinical phenotype.
超过150种单基因癫痫的发现以及早期基因诊断技术的进步，引发了人们对逆转甚至预防这些使人衰弱的脑部疾病进程的分子策略和发育时间表的探索。关键疾病基因的直系同源啮齿动物模型为靶点范围提供了重要示例，并作为围产期治疗方法的宝贵测试系统。虽然对单一罕见“孤儿”疾病的基因特异性分析范围都很狭窄，但它们揭示了汇聚到中间神经元的下游通路，而在皮层成熟过程中增强抑制作用的治疗方法可能为这些看似不同的基因错误提供广泛的保护。有几种基因，即使是那些与畸形相关的基因，在其临床表型出现之前进行产后纠正也显示出希望。
