再髓鞘化
多发性硬化
髓鞘
高分辨率
神经科学
计算生物学
纳米技术
计算机科学
高通量筛选
生物
吞吐量
材料科学
生物信息学
免疫学
中枢神经系统
电信
遥感
无线
地质学
作者
Feng Mei,Stephen P.J. Fancy,Yu‐Chu Shen,Jianqin Niu,Chao Zhao,Bryan Presley,Edna Miao,Seonok Lee,Sonia R. Mayoral,Stephanie Redmond,Ainhoa Etxeberría,Lan Xiao,Robin J.M. Franklin,Ari Green,Stephen L. Hauser,Jonah R. Chan
出处
期刊:Nature Medicine
[Springer Nature]
日期:2014-07-06
卷期号:20 (8): 954-960
被引量:448
摘要
High-throughput screening platform for the testing of small bioactive molecules that promote oligodendrocyte differentiation and remyelination: a new path to the discovery of potential drugs for multiple sclerosis. Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.
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