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Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation
Dedicator of cytokinesis 3 (DOCK3) is an atypical member of the guanine nucleotide exchange factors (GEFs) and plays important roles in neurite outgrowth. DOCK3 forms a complex with Engulfment and cell motility protein 1 (Elmo1) and effectively activates Rac1 and actin dynamics. In this study, we sc...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10184973/ https://www.ncbi.nlm.nih.gov/pubmed/37188749 http://dx.doi.org/10.1038/s41420-023-01460-8 |
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author | Namekata, Kazuhiko Tsuji, Naoki Guo, Xiaoli Nishijima, Euido Honda, Sari Kitamura, Yuta Yamasaki, Atsushi Kishida, Masamichi Takeyama, Jun Ishikawa, Hirokazu Shinozaki, Youichi Kimura, Atsuko Harada, Chikako Harada, Takayuki |
author_facet | Namekata, Kazuhiko Tsuji, Naoki Guo, Xiaoli Nishijima, Euido Honda, Sari Kitamura, Yuta Yamasaki, Atsushi Kishida, Masamichi Takeyama, Jun Ishikawa, Hirokazu Shinozaki, Youichi Kimura, Atsuko Harada, Chikako Harada, Takayuki |
author_sort | Namekata, Kazuhiko |
collection | PubMed |
description | Dedicator of cytokinesis 3 (DOCK3) is an atypical member of the guanine nucleotide exchange factors (GEFs) and plays important roles in neurite outgrowth. DOCK3 forms a complex with Engulfment and cell motility protein 1 (Elmo1) and effectively activates Rac1 and actin dynamics. In this study, we screened 462,169 low-molecular-weight compounds and identified the hit compounds that stimulate the interaction between DOCK3 and Elmo1, and neurite outgrowth in vitro. Some of the derivatives from the hit compound stimulated neuroprotection and axon regeneration in a mouse model of optic nerve injury. Our findings suggest that the low-molecular-weight DOCK3 activators could be a potential therapeutic candidate for treating axonal injury and neurodegenerative diseases including glaucoma. |
format | Online Article Text |
id | pubmed-10184973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101849732023-05-16 Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation Namekata, Kazuhiko Tsuji, Naoki Guo, Xiaoli Nishijima, Euido Honda, Sari Kitamura, Yuta Yamasaki, Atsushi Kishida, Masamichi Takeyama, Jun Ishikawa, Hirokazu Shinozaki, Youichi Kimura, Atsuko Harada, Chikako Harada, Takayuki Cell Death Discov Article Dedicator of cytokinesis 3 (DOCK3) is an atypical member of the guanine nucleotide exchange factors (GEFs) and plays important roles in neurite outgrowth. DOCK3 forms a complex with Engulfment and cell motility protein 1 (Elmo1) and effectively activates Rac1 and actin dynamics. In this study, we screened 462,169 low-molecular-weight compounds and identified the hit compounds that stimulate the interaction between DOCK3 and Elmo1, and neurite outgrowth in vitro. Some of the derivatives from the hit compound stimulated neuroprotection and axon regeneration in a mouse model of optic nerve injury. Our findings suggest that the low-molecular-weight DOCK3 activators could be a potential therapeutic candidate for treating axonal injury and neurodegenerative diseases including glaucoma. Nature Publishing Group UK 2023-05-15 /pmc/articles/PMC10184973/ /pubmed/37188749 http://dx.doi.org/10.1038/s41420-023-01460-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Namekata, Kazuhiko Tsuji, Naoki Guo, Xiaoli Nishijima, Euido Honda, Sari Kitamura, Yuta Yamasaki, Atsushi Kishida, Masamichi Takeyama, Jun Ishikawa, Hirokazu Shinozaki, Youichi Kimura, Atsuko Harada, Chikako Harada, Takayuki Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title | Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title_full | Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title_fullStr | Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title_full_unstemmed | Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title_short | Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation |
title_sort | neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of dock3 conformation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10184973/ https://www.ncbi.nlm.nih.gov/pubmed/37188749 http://dx.doi.org/10.1038/s41420-023-01460-8 |
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