Year: 2022
Type: article
Abstract: The sigma 2 receptor (σ2R) was recently identified as an ER (endoplasmic reticulum) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that compounds that bind to σ2R/TMEM97 are neuroprotective, suggesting that σ2R/TMEM97 is involved in pathways leading to neurodegeneration. We explore the role of σ2R/TMEM97 in neurodegeneration by characterizing ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97−/− mice and demonstrate that in the absence of σ2R/TMEM97, RGCs are resistant to degeneration. In addition, we show that DKR-1677, a selective σ2R/TMEM97 ligand, significantly protects RGCs from ischemia-induced degeneration in wildtype mice. These results provide conclusive evidence that σ2R/TMEM97 plays a significant role in RGC death to facilitate neurodegeneration following ischemic injury. Blocking the function of σ2R/TMEM97 thus is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ2R/TMEM97 in RGCs and likely in other σ2R/TMEM97-expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches to treat RGC degenerative diseases by inhibiting σ2R/TMEM97.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,190
Funders: Welch Foundation, Research to Prevent Blindness, Hope For Vision, National Institutes of Health, University of North Carolina at Chapel Hill, Dell Medical School, University of Texas at Austin, National Institute of Mental Health, National Eye Institute, National Institute of Neurological Disorders and Stroke, Office of Extramural Research, National Institutes of Health
Awards: Role of astrocytic TNF receptor 2 in synaptic stability and cognitive function after traumatic brain injury, G122280911, G1781497540, G1915163810, Quantitative multimodal retinal imaging, G3515711078, G4005454282, G4200407693, Imaging the functional biomarker of photoreceptors, DHDDS and Retinal Degeneration, G5530041803, G6867265530, G8054139820, G8572998776, Stabilizing the Tripartite Synaptic Complex Following TBI, Miami Center for Vision Research
OpenAlex ID: W4310708829