Synapse microarray identification of small molecules that enhance synaptogenesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Mark A. Scott
  • Balaram Ghosh
  • Dongpeng Wan
  • Zachary Wissner-Gross
  • Ralph Mazitschek
  • Stephen J. Haggarty
  • Mehmet Fatih Yanik

Detail(s)

Original languageEnglish
Article number510
Journal / PublicationNature Communications
Volume2
Issue number1
Publication statusPublished - 2011

Abstract

Synaptic function is affected in many brain diseases and disorders. Technologies for large-scale synapse assays can facilitate identification of drug leads. Here we report a 'synapse microarray' technology that enables ultra-sensitive, high-throughput and quantitative screening of synaptogenesis. Our platform enables the induction of synaptic structures in regular arrays by precise positioning of non-neuronal cells expressing synaptic proteins, while allowing neurites to grow freely around these cells. The technology increases by tenfold the sensitivity of the traditional assays, and simultaneously decreases the time required to capture synaptogenic events by an order of magnitude. It is readily incorporated into multiwell formats compatible with industrial high-throughput screening platforms. Using this technology, we screened a chemical library, and identified novel histone deacetylase (HDAC) inhibitors that improve neuroligin-1-induced synaptogenesis by modulating class-I HDACs. We also found a structureĝ€"activity relationship for designing novel potent histone deacetylase inhibitors, which can be applied towards development of new therapeutics. © 2011 Macmillan Publishers Limited. All rights reserved.

Citation Format(s)

Synapse microarray identification of small molecules that enhance synaptogenesis. / Shi, Peng; Scott, Mark A.; Ghosh, Balaram; Wan, Dongpeng; Wissner-Gross, Zachary; Mazitschek, Ralph; Haggarty, Stephen J.; Yanik, Mehmet Fatih.

In: Nature Communications, Vol. 2, No. 1, 510, 2011.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review