Sigma receptors are present on the neurons of the central nervous system and in peripheral organs. They have also been demonstrated in ocular tissues by in vitro membrane binding assays. We have investigated whether sigma(1) receptors can be demonstrated in rat eyes by ex vivo autoradiography using [(11)C]SA4503, a selective radioligand. We also tested whether in vivo positron emission tomography (PET) can be used to show sigma(1) receptors in rabbit eyes. In rats, a high accumulation of [(11)C]SA4503 was found in the iris-ciliary body and retina. A carrier-loading experiment showed that the receptor-specific binding of [(11)C]SA4503 was approximately 75% of the total binding in the brain. Sigma(1) receptors were also detected in the projecting terminals of the retina to the superior colliculus. PET showed radioactivity in the anterior segment including the iris-ciliary body and retina, and pretreatment or displacement by a sigma receptor ligand (haloperidol), suggested that the PET signal reflects radioligand-receptor binding. The high density of sigma(1) receptors in the iris-ciliary body and retina was confirmed by ex vivo autoradiography. In conclusion, the iris-ciliary body and retina are rich in sigma(1) receptors, and PET may be used to investigate the in vivo distribution of these neuroreceptors in the eye.
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http://dx.doi.org/10.1006/exer.2002.2048 | DOI Listing |
Biomed Pharmacother
December 2024
Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing, Chulalongkorn University, Bangkok 10330, Thailand; Research, Innovation and International Affairs, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand. Electronic address:
Model organisms are commonly used to study human diseases; we set out to understand the relevance of several model organisms with relation to the σ1R protein. The study explored the interactions of σ1R with various agonists, antagonists across different species. Ligand and protein-protein (σ1R-BiP) docking approaches were used to understand the significance of σ1R in modulating neuroprotective mechanisms and its potential role in Alzheimer's.
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Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia.
As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins.
View Article and Find Full Text PDFAnal Chem
December 2024
Instituto de Biomedicina y Genética Molecular, Unidad de Excelencia, University of Valladolid-CSIC, Valladolid 47003, Spain.
Lipid rafts are liquid-ordered domains in which specific enzymes and receptors are located. These membrane platforms play crucial roles in a variety of signaling pathways. Alterations in the lipid environment, such as those elicited by oxidative stress, can lead to important functional disruptions in membrane proteins.
View Article and Find Full Text PDFEur J Pain
January 2025
Inserm U987, UVSQ, Paris-Saclay University, Ambroise-Paré Hospital, Boulogne-Billancourt, France.
Developing sigma-1 receptor (S1R) modulators is considered a valuable therapeutic strategy to counteract neurodegeneration, cancer progression, and viral infections, including COVID-19. In this context, tools capable of accurately predicting S1R affinity are highly desirable. Herein, we present a panel of 25 classifiers trained on a curated dataset of high-quality bioactivity data of small molecules, experimentally tested as potential S1R modulators.
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