{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang H"],"funding":["Dell Medical School, University of Texas at Austin","Miami Project to Cure Paralysis","Office of Extramural Research, National Institutes of Health","Welch Foundation","Hope For Vision"],"pagination":["20753"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9715665"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["The sigma 2 receptor (σ<sub>2</sub>R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ<sub>2</sub>R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ<sub>2</sub>R/TMEM97 in neurodegenerative processes. To understand the function of σ<sub>2</sub>R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97<sup>-/-</sup> mice and found that RGCs in TMEM97<sup>-/-</sup> mice are resistant to degeneration. In addition, intravitreal injection of a selective σ<sub>2</sub>R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ<sub>2</sub>R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ<sub>2</sub>R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ<sub>2</sub>R/TMEM97 in RGCs and likely in other σ<sub>2</sub>R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ<sub>2</sub>R/TMEM97."],"journal":["Scientific reports"],"pubmed_title":["σ<sub>2</sub>R/TMEM97 in retinal ganglion cell degeneration."],"pmcid":["PMC9715665"],"funding_grant_id":["Grant","Support","R01EY023666; R01EY026643; R01EY031492; P30EY14801; NS098740; NS120028;","F-0652","Texas Health Catalyst program"],"pubmed_authors":["Chou TH","Martin SF","Liebl DJ","Liu Q","Wang H","Wen R","Zhou X","Peng Z","Li Y","Sahn JJ","Jiao S","Porciatti V","Hodges TR"],"additional_accession":[]},"is_claimable":false,"name":"σ<sub>2</sub>R/TMEM97 in retinal ganglion cell degeneration.","description":"The sigma 2 receptor (σ<sub>2</sub>R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ<sub>2</sub>R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ<sub>2</sub>R/TMEM97 in neurodegenerative processes. To understand the function of σ<sub>2</sub>R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97<sup>-/-</sup> mice and found that RGCs in TMEM97<sup>-/-</sup> mice are resistant to degeneration. In addition, intravitreal injection of a selective σ<sub>2</sub>R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ<sub>2</sub>R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ<sub>2</sub>R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ<sub>2</sub>R/TMEM97 in RGCs and likely in other σ<sub>2</sub>R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ<sub>2</sub>R/TMEM97.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-25T17:09:23.389Z","creation":"2025-04-06T05:03:42.597Z"},"accession":"S-EPMC9715665","cross_references":{"pubmed":["36456686"],"doi":["10.1038/s41598-022-24537-3"]}}