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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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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. |
format | Online Article Text |
id | pubmed-3544154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
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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