Cellular Reprogramming: Recent Advances in Modeling Neurological Diseases
Cellular Reprogramming: Recent Advances in Modeling Neurological Diseases
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DOI：
10.1523/jneurosci.4218-11.2011
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发表时间：
2011-11-09
影响因子：
5.3
通讯作者：
Christian, Kimberly M.
中科院分区：
文献类型：
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作者：
Ming, Guo-Li;Bruestle, Oliver;Christian, Kimberly M.
细胞重编程的显著进展使得从新生儿和成人皮肤样品获得的成纤维细胞产生人类神经元的可再生来源成为可能。因此，我们现在可以使用来自患者的神经元群体在细胞水平上研究神经系统疾病的病因，这些神经元群体具有被认为与病理风险相关的相同基因突变。治疗意义包括建立新的人源化疾病模型以了解机制的能力，对新的生物源化合物进行高通量筛选以逆转或预防疾病表型，鉴定和工程化因果突变的遗传拯救，以及开发患者特异性细胞替代策略。尽管这一领域为理解和治疗神经系统疾病提供了巨大的潜力，但在我们充分利用这项技术之前，仍然有许多问题必须解决。在这里，我们总结了最近在神经科学学会2011年年会的研讨会上提出的几项研究，这些研究强调了细胞重编程的创新方法，以及这种革命性的技术是如何被改进以模拟神经发育和神经退行性疾病，如自闭症谱系障碍，精神分裂症，家族性自主神经功能障碍和阿尔茨海默病。
The remarkable advances in cellular reprogramming have made it possible to generate a renewable source of human neurons from fibroblasts obtained from skin samples of neonates and adults. As a result, we can now investigate the etiology of neurological diseases at the cellular level using neuronal populations derived from patients, which harbor the same genetic mutations thought to be relevant to the risk for pathology. Therapeutic implications include the ability to establish new humanized disease models for understanding mechanisms, conduct high-throughput screening for novel biogenic compounds to reverse or prevent the disease phenotype, identify and engineer genetic rescue of causal mutations, and develop patient-specific cellular replacement strategies. Although this field offers enormous potential for understanding and treating neurological disease, there are still many issues that must be addressed before we can fully exploit this technology. Here we summarize several recent studies presented at a symposium at the 2011 annual meeting of the Society for Neuroscience, which highlight innovative approaches to cellular reprogramming and how this revolutionary technique is being refined to model neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorders, schizophrenia, familial dysautonomia, and Alzheimer's disease.