Repairing DNA damages in neurodegenerative diseases

Parkin基因突变体未能泛化细胞周期蛋白E，导致细胞周期紊乱。我们已经发现了Parkin突变体泛化细胞周期蛋白E的核途径，从而可能控制细胞周期，促进细胞存活。我们的观察可能为反义介导的治疗程序的发展提供分子基础，该程序将是特异的、合理的和基于基因的。在脊髓小脑型共济失调中，致病基因突变型蛋白激酶Cγ可抑制隐性共济失调相关的aprataxin的核进入。核内凋亡素的减少增加了氧化应激诱导的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.