A central and causative feature of age-related neurodegenerative disease is the deposition of misfolded proteins in the brain. To devise novel approaches to treatment, regulatory pathways that modulate these aggregation-prone proteins must be defined. One such pathway is post-translational modification by the addition of poly(ADP-ribose) (PAR), which promotes protein recruitment and localization in several cellular contexts. Mounting evidence implicates PAR in seeding the abnormal localization and accumulation of proteins that are causative of neurodegenerative disease. Inhibitors of PAR polymerase (PARP) activity have been developed as cancer therapeutics, raising the possibility that they could be used to treat neurodegenerative disease. We focus on pathways regulated by PAR in neurodegenerative disease, with emphasis on amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD).

与年龄有关的神经退行性疾病的主要和成因特征是错误折叠的蛋白质在大脑中的沉积。为了设计新颖的治疗方法，必须定义调节这些易于聚集蛋白的调节途径。一种这样的途径是通过添加聚（ADP-核糖）（PAR）的翻译后修饰，其在几种细胞环境中促进蛋白质募集和定位。越来越多的证据表明，PAR可能是导致神经退行性疾病的蛋白质异常定位和积累的种子。已经开发出PAR聚合酶（PARP）活性抑制剂作为癌症治疗剂，从而增加了它们可用于治疗神经退行性疾病的可能性。我们专注于神经退行性疾病中受PAR调节的途径，