Abstract：
Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia\'s encephalopathy), and BSCL2-associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by BSCL2 gene mutations.
摘要：
Seipin,由Berardinelli-Seip先天性脂肪营养不良2型（BSCL2）基因编码的蛋白质，以其在脂滴和2型先天性全身性脂肪营养不良（CGL2）的生物发生中的关键作用而闻名。BSCL2基因突变导致遗传性疾病，包括CGL2，进行性脑病伴或不伴脂肪营养不良（也称为西莉亚脑病），和BSCL2相关的运动神经元疾病。在肝脂肪变性中也发现了seipin的异常表达，神经退行性疾病，胶质母细胞瘤中风，心脏肥大,和其他疾病。在目前的研究中,我们全面总结了表型，潜在机制，和治疗由BSCL2基因突变引起的人类疾病，同时进行动物研究，包括系统性或特异性Bscl2基因敲除，或Bscl2基因过表达。在代表与Bscl2突变无关的疾病的各种动物模型中，还描述了seipin的差异表达模式和功能作用。此外，我们通过靶向seipin或其上游和下游信号通路来强调潜在的治疗方法。一起来看,恢复脂肪组织功能和靶向seipin相关通路是CGL2治疗的有效策略。同时,同时,也认为seipin相关通路在非BSCL2基因突变引起的疾病中具有潜在的治疗价值。
