Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.
Exp Biol Med (Maywood). 2013 Mar;238(3):301-7. doi: 10.1177/1535370213480703.
The ataxia telangiectasia mutated (ATM) kinase is a key transducer of the cellular response to DNA double strand breaks and its deficiency causes ataxia-telangiectasia (A-T), a pleiotropic genetic disorder primarily characterized by cerebellar neuropathy, immunodeficiency and cancer predisposition. While enormous progress has been achieved in elucidating the biochemical and functional regulation of ATM in DNA damage response, and more recently in redox signalling and antioxidant defence, the factors that make neurons in A-T extremely vulnerable remain unclear. Given also that ATM knockout mice do not recapitulate the central nervous system phenotype, a number of human neural stem cell (hNSC) model systems have been developed to provide insights into the mechanisms of neurodegeneration associated with ATM dysfunction. Here we review the hNSC systems developed by us an others to model A-T.
共济失调毛细血管扩张突变（ATM）激酶是细胞对 DNA 双链断裂反应的关键转导因子，其缺陷导致共济失调毛细血管扩张症（A-T），这是一种多系统遗传疾病，主要表现为小脑神经病、免疫缺陷和易患癌症。虽然在阐明 ATM 在 DNA 损伤反应中的生化和功能调节方面已经取得了巨大进展，并且最近在氧化还原信号和抗氧化防御方面也取得了进展，但使 A-T 神经元极其脆弱的因素仍不清楚。鉴于 ATM 敲除小鼠不能重现中枢神经系统表型，已经开发了许多人类神经干细胞（hNSC）模型系统，以深入了解与 ATM 功能障碍相关的神经退行性变机制。在这里，我们综述了我们和其他人开发的用于模拟 A-T 的 hNSC 系统。
