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Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays

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. O...

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Detalles Bibliográficos
Autores principales: Shi, Peng, Scott, Mark A, Ghosh, Balaram, Wan, Dongpeng, Wissner-Gross, Zachary, Mazitschek, Ralph, Haggarty, Stephen J., Yanik, Mehmet Fatih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544154/
https://www.ncbi.nlm.nih.gov/pubmed/22027590
http://dx.doi.org/10.1038/ncomms1518
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author Shi, Peng
Scott, Mark A
Ghosh, Balaram
Wan, Dongpeng
Wissner-Gross, Zachary
Mazitschek, Ralph
Haggarty, Stephen J.
Yanik, Mehmet Fatih
author_facet Shi, Peng
Scott, Mark A
Ghosh, Balaram
Wan, Dongpeng
Wissner-Gross, Zachary
Mazitschek, Ralph
Haggarty, Stephen J.
Yanik, Mehmet Fatih
author_sort Shi, Peng
collection PubMed
description 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 inhibitors that improve neuroligin-1 induced synaptogenesis via modulating class-I histone deacetylases. We also found a structure-activity relationship for designing novel potent histone deacetylase inhibitors, which can be applied towards development of new therapeutics.
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spelling pubmed-35441542013-01-14 Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays Shi, Peng Scott, Mark A Ghosh, Balaram Wan, Dongpeng Wissner-Gross, Zachary Mazitschek, Ralph Haggarty, Stephen J. Yanik, Mehmet Fatih Nat Commun Article 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 inhibitors that improve neuroligin-1 induced synaptogenesis via modulating class-I histone deacetylases. We also found a structure-activity relationship for designing novel potent histone deacetylase inhibitors, which can be applied towards development of new therapeutics. 2011-10-25 /pmc/articles/PMC3544154/ /pubmed/22027590 http://dx.doi.org/10.1038/ncomms1518 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shi, Peng
Scott, Mark A
Ghosh, Balaram
Wan, Dongpeng
Wissner-Gross, Zachary
Mazitschek, Ralph
Haggarty, Stephen J.
Yanik, Mehmet Fatih
Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title_full Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title_fullStr Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title_full_unstemmed Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title_short Identification of small molecules that Enhance Synaptogenesis using Synapse Microarrays
title_sort identification of small molecules that enhance synaptogenesis using synapse microarrays
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544154/
https://www.ncbi.nlm.nih.gov/pubmed/22027590
http://dx.doi.org/10.1038/ncomms1518
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