| Literature DB >> 24997607 |
Feng Mei1, Stephen P J Fancy1,2, Yun-An A Shen1, Jianqin Niu3, Chao Zhao4, Bryan Presley5, Edna Miao1, Seonok Lee1, Sonia R Mayoral1, Stephanie A Redmond1, Ainhoa Etxeberria1, Lan Xiao3, Robin J M Franklin4, Ari Green1, Stephen L Hauser1, Jonah R Chan1.
Abstract
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.Entities:
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Year: 2014 PMID： 24997607 PMCID： PMC4830134 DOI： 10.1038/nm.3618
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440