Defective repair of neuronal activity-induced DNA double strand breaks: A novel pathogenic mechanism for neurodegeneration in ataxia-telangiectasia

共济失调-毛细血管扩张患者后脑变性的原因尚不清楚。神经元放电导致正常由ATM修复的DNA断裂，ATM是共济失调毛细血管扩张症的基因缺陷，而系统复位失败可能导致基因异常表达和细胞死亡。在这里，我们使用来自患者干细胞的神经细胞类型来阐明这种新的疾病机制是如何导致后脑变性的，并测试可以克服这种疾病的药物。

The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.