Repairing DNA damages in neurodegenerative diseases

Parkin基因突变体不能泛素化cyclin E，导致细胞周期失调。我们已经发现了帕金突变体泛素化细胞周期蛋白E的核途径，从而控制细胞周期，有助于细胞存活。我们的观察可能提供一个分子基础的反义介导的治疗程序，将是具体的，合理的，遗传为基础的发展。在脊髓小脑性共济失调（SCA 14）中，致病基因突变体蛋白激酶C γ可抑制与隐性共济失调相关的aprataxin进入细胞核。减少核aprataxin增加氧化应激诱导的DNA损伤和细胞死亡。

Parkin gene mutant failed to ubiquitinate cyclin E, leading to cell cycle deregulation. We has uncovered the nuclear pathway by which the Parkin mutant ubiqutinates cyclin E and may thus control the cell cycle, contributing to cell survival. Our observations may provide a molecular basis for the development of an antisense-mediated therapeutic procedure that would be specific, rational, and genetically based. In spinocerebellar ataxia (SCA14), causative gene mutant ProteinkinaseCγcaused to inhibit the nuclear entry of recessive-ataxia-related aprataxin. Decreased nuclear aprataxin increased oxidative stress-induced DNA damage and cell death.