Wong Maggie M K, Watson Lauren M, Becker Esther B E
Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom.
J Neurol Neuromedicine. 2017 Jul 10;2(7):11-15. doi: 10.29245/2572.942x/2017/7.1134.
The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to model cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.
小脑性共济失调是一组无法治愈的脑部疾病，主要由小脑浦肯野细胞的进行性功能障碍和退化引起。针对异质性共济失调缺乏可靠的疾病模型，这阻碍了对潜在致病机制的理解以及针对这些毁灭性疾病的有效疗法的开发。诱导多能干细胞（iPSC）技术领域的最新进展为更好地理解并潜在地逆转疾病病理提供了新的可能性。鉴于在几种类型的共济失调中观察到神经发育表型，基于iPSC的模型有潜力为疾病进展提供重要见解，也为早期干预疗法的开发提供机会。然而，迄今为止，很少有研究成功地使用iPSC衍生细胞来模拟小脑性共济失调。在这篇综述中，我们重点关注生成人iPSC衍生浦肯野细胞的最新突破。我们还强调了为充分利用这些模型来模拟小脑性共济失调的分子机制以及开发有效治疗方法而需要解决的未来挑战。
