神经障碍患者的纤维母细胞直接转换成神经细胞的临床应用: 溶酶体贮积症和离子通道病的研究

Title:Clinical Utility of Neuronal Cells Directly Converted from Fibroblasts of Patients for Neuropsychiatric Disorders: Studies of Lysosomal Storage Diseases and Channelopathy

Volume: 15 Issue: 2

关键词: 直接转化，诱导神经元细胞，iN 细胞，溶酶体贮积症，离子通道病；多聚谷氨酰胺疾病

摘要: Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies.

Cite this article as:

Clinical Utility of Neuronal Cells Directly Converted from Fibroblasts of Patients for Neuropsychiatric Disorders: Studies of Lysosomal Storage Diseases and Channelopathy, Current Molecular Medicine 2015; 15 (2) . https://dx.doi.org/10.2174/1566524015666150303110300