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σ(2)R/TMEM97 in retinal ganglion cell degeneration
The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understa...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715665/ https://www.ncbi.nlm.nih.gov/pubmed/36456686 http://dx.doi.org/10.1038/s41598-022-24537-3 |
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author | Wang, Hua Peng, Zhiyou Li, Yiwen Sahn, James J. Hodges, Timothy R. Chou, Tsung-Han Liu, Qiong Zhou, Xuezhi Jiao, Shuliang Porciatti, Vittorio Liebl, Daniel J. Martin, Stephen F. Wen, Rong |
author_facet | Wang, Hua Peng, Zhiyou Li, Yiwen Sahn, James J. Hodges, Timothy R. Chou, Tsung-Han Liu, Qiong Zhou, Xuezhi Jiao, Shuliang Porciatti, Vittorio Liebl, Daniel J. Martin, Stephen F. Wen, Rong |
author_sort | Wang, Hua |
collection | PubMed |
description | The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understand the function of σ(2)R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97(−/−) mice and found that RGCs in TMEM97(−/−) mice are resistant to degeneration. In addition, intravitreal injection of a selective σ(2)R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ(2)R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ(2)R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ(2)R/TMEM97 in RGCs and likely in other σ(2)R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ(2)R/TMEM97. |
format | Online Article Text |
id | pubmed-9715665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97156652022-12-03 σ(2)R/TMEM97 in retinal ganglion cell degeneration Wang, Hua Peng, Zhiyou Li, Yiwen Sahn, James J. Hodges, Timothy R. Chou, Tsung-Han Liu, Qiong Zhou, Xuezhi Jiao, Shuliang Porciatti, Vittorio Liebl, Daniel J. Martin, Stephen F. Wen, Rong Sci Rep Article The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understand the function of σ(2)R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97(−/−) mice and found that RGCs in TMEM97(−/−) mice are resistant to degeneration. In addition, intravitreal injection of a selective σ(2)R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ(2)R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ(2)R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ(2)R/TMEM97 in RGCs and likely in other σ(2)R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ(2)R/TMEM97. Nature Publishing Group UK 2022-12-01 /pmc/articles/PMC9715665/ /pubmed/36456686 http://dx.doi.org/10.1038/s41598-022-24537-3 Text en © The Author(s) 2022 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Hua Peng, Zhiyou Li, Yiwen Sahn, James J. Hodges, Timothy R. Chou, Tsung-Han Liu, Qiong Zhou, Xuezhi Jiao, Shuliang Porciatti, Vittorio Liebl, Daniel J. Martin, Stephen F. Wen, Rong σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title | σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title_full | σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title_fullStr | σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title_full_unstemmed | σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title_short | σ(2)R/TMEM97 in retinal ganglion cell degeneration |
title_sort | σ(2)r/tmem97 in retinal ganglion cell degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715665/ https://www.ncbi.nlm.nih.gov/pubmed/36456686 http://dx.doi.org/10.1038/s41598-022-24537-3 |
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