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Sigma-1 receptor

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https://www.readbyqxmd.com/read/28932185/hyperactivity-of-hypothalamic-pituitary-adrenal-axis-due-to-dysfunction-of-the-hypothalamic-glucocorticoid-receptor-in-sigma-1-receptor-knockout-mice
#1
Tingting Di, Suyun Zhang, Juan Hong, Tingting Zhang, Ling Chen
Sigma-1 receptor knockout (σ1R-KO) mice exhibit a depressive-like phenotype. Because σ1R is highly expressed in the neuronal cells of hypothalamic paraventricular nuclei (PVN), this study investigated the influence of σ1R deficiency on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Here, we show that the levels of basal serum corticosterone (CORT), adrenocorticotropic hormone (ACTH) and corticotrophin releasing factor (CRF) as well as the level of CRF mRNA in PVN did not significantly differ between adult male σ1R-KO mice and wild-type (WT) mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28931430/global-proteomic-profiling-of-yersinia-ruckeri-strains
#2
Gokhlesh Kumar, Karin Hummel, Timothy J Welch, Ebrahim Razzazi-Fazeli, Mansour El-Matbouli
Yersinia ruckeri is the causative agent of enteric redmouth disease (ERM) of salmonids. There is little information regarding the proteomics of Y. ruckeri. Herein, we perform whole protein identification and quantification of biotype 1 and biotype 2 strains of Y. ruckeri grown under standard culture conditions using a shotgun proteomic approach. Proteins were extracted, digested and peptides were separated by a nano liquid chromatography system and analyzed with a high-resolution hybrid triple quadrupole time of flight mass spectrometer coupled via a nano ESI interface...
September 20, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28927431/role-of-the-sigma-1-receptor-chaperone-in-rod-and-cone-photoreceptor-degenerations-in-a-mouse-model-of-retinitis-pigmentosa
#3
Huan Yang, Yingmei Fu, Xinying Liu, Pawan K Shahi, Timur A Mavlyutov, Jun Li, Annie Yao, Steven Z-W Guo, Bikash R Pattnaik, Lian-Wang Guo
BACKGROUND: Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones. The mechanisms underlying the S1R protection for cones are not understood in detail...
September 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28924870/efficacy-of-a-novel-sigma-1-receptor-antagonist-for-oxaliplatin-induced-neuropathy-a-randomized-double-blind-placebo-controlled-phase-iia-clinical-trial
#4
Jordi Bruna, Sebastián Videla, Andreas A Argyriou, Roser Velasco, Jesús Villoria, Cristina Santos, Cristina Nadal, Guido Cavaletti, Paola Alberti, Chiara Briani, Haralabos P Kalofonos, Diego Cortinovis, Mariano Sust, Anna Vaqué, Thomas Klein, Carlos Plata-Salamán
This trial assessed the efficacy of MR309 (a novel selective sigma-1 receptor ligand previously developed as E-52862) in ameliorating oxaliplatin-induced peripheral neuropathy (oxaipn). A discontinuous regimen of MR309 (400 mg/day, 5 days per cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. Outcome measures included changes in 24-week quantitative measures of thermal sensitivity and total neuropathy score...
September 18, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#5
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916283/deuterated-d6-dextromethorphan-elicits-antidepressant-like-effects-in-mice
#6
Linda Nguyen, Anna L Scandinaro, Rae R Matsumoto
The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy...
September 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28912535/molecular-mechanisms-underlying-the-involvement-of-the-sigma-1-receptor-in-methamphetamine-mediated-microglial-polarization
#7
Jie Chao, Yuan Zhang, Longfei Du, Rongbin Zhou, Xiaodong Wu, Kai Shen, Honghong Yao
Our previous study demonstrated that the sigma-1 receptor is involved in methamphetamine-induced microglial apoptosis and death; however, whether the sigma-1 receptor is involved in microglial activation as well as the molecular mechanisms underlying this process remains poorly understood. The aim of this study is to demonstrate the involvement of the sigma-1 receptor in methamphetamine-mediated microglial activation. The expression of σ-1R, iNOS, arginase and SOCS was examined by Western blot; activation of cell signaling pathways was detected by Western blot analysis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898265/sigma-1-receptor-regulates-erk-activation-and-promotes-survival-of-optic-nerve-head-astrocytes
#8
Jing Zhao, Barbara A Mysona, Jing Wang, Graydon B Gonsalvez, Sylvia B Smith, Kathryn E Bollinger
The sigma 1 receptor (S1R) is a unique transmembrane protein that has been shown to regulate neuronal differentiation and cellular survival. It is expressed within several cell types throughout the nervous system and visceral organs, including neurons and glia within the eye. S1R ligands are therapeutic targets for diseases ranging from neurodegenerative conditions to neoplastic disorders. However, effects of S1R activation and inhibition within glia cells are not well characterized. Within the eye, the astrocytes at the optic nerve head are crucial to the health and survival of the neurons that send visual information to the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28890198/crosstalk-between-endoplasmic-reticulum-stress-and-oxidative-stress-in-schizophrenia-the-dawn-of-new-therapeutic-approaches
#9
REVIEW
Shivangi Patel, Dilip Sharma, Kiran Kalia, Vinod Tiwari
Disruption of oxidant/anti-oxidant ratio as well as endoplasmic reticulum (ER) stress are thought to be involved in the pathophysiology of schizophrenia. These stresses can lead to impairments in brain functions progressively leading to neuronal inflammation followed by neuronal cell death. Moreover, the cellular stresses are interlinked leading us to the conclusion that protein misfolding, oxidative stress and apoptosis are intricately intertwined events requiring further research into their mechanistic and physiological pathways...
September 7, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28883901/loss-of-sigma-1-receptor-chaperone-promotes-astrocytosis-and-enhances-the-nrf2-antioxidant-defense
#10
Tzu-Yu Weng, Denise T Hung, Tsung-Ping Su, Shang-Yi A Tsai
Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28881650/apex2-enhanced-electron-microscopy-distinguishes-sigma-1-receptor-localization-in-the-nucleoplasmic-reticulum
#11
Timur A Mavlyutov, Huan Yang, Miles L Epstein, Arnold E Ruoho, Jay Yang, Lian-Wang Guo
The sigma-1 receptor (Sig1R) is an endoplasmic reticulum chaperonin that is attracting tremendous interest as a potential anti-neurodegenerative target. While this membrane protein is known to reside in the inner nuclear envelope (NE) and influences transcription, apparent Sig1R presence in the nucleoplasm is often observed, seemingly contradicting its NE localization. We addressed this confounding issue by applying an antibody-free approach of electron microscopy (EM) to define Sig1R nuclear localization. We expressed APEX2 peroxidase fused to Sig1R-GFP in a Sig1R-null NSC34 neuronal cell line generated with CRISPR-Cas9...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877319/absence-of-sigma-1-receptor-accelerates-photoreceptor-cell-death-in-a-murine-model-of-retinitis-pigmentosa
#12
Jing Wang, Alan Saul, Xuezhi Cui, Penny Roon, Sylvia B Smith
Purpose: Sigma 1 Receptor (Sig1R) is a novel therapeutic target in neurodegenerative diseases, including retinal disease. Sig1R-/- mice have late-onset retinal degeneration with ganglion cell loss that worsens under stress. Whether Sig1R plays a role in maintaining other retinal neurons is unknown, but was investigated here using rd10 mice, a model of severe photoreceptor degeneration. Methods: Wild-type, rd10, and rd10/Sig1R-/- mice were subjected to ERG and spectral-domain optical coherence tomography (SD-OCT) to assess visual function/structure in situ...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28871306/introduction-to-sigma-proteins-evolution-of-the-concept-of-sigma-receptors
#13
Felix J Kim
For over 40 years, scientists have endeavored to understand the so-called sigma receptors. During this time, the concept of sigma receptors has continuously and significantly evolved. With thousands of publications on the subject, these proteins have been implicated in various diseases, disorders, and physiological processes. Nevertheless, we are just beginning to understand what sigma proteins do and how they work. Two subtypes have been identified, Sigma1 and Sigma2. Whereas Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor, and several other names) was cloned over 20 years ago, Sigma2 (sigma-2 receptor, σ2 receptor) was cloned very recently and had remained a pharmacologically defined entity...
September 5, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28870519/sigma-1-receptor-knockout-increases-%C3%AE-synuclein-aggregation-and-phosphorylation-with-loss-of-dopaminergic-neurons-in-substantia-nigra
#14
Juan Hong, Ling Wang, Tingting Zhang, Baofeng Zhang, Ling Chen
Sigma-1 receptor (σ1R) is expressed in dopaminergic neurons of substantia nigra. Here, we show that σ1R knockout (σ1R(-/-)) mice, at age 6-12 months, appeared with age-related loss of dopaminergic neurons and decline of motor coordination. Levels of α-synuclein (αSyn) oligomers and fibrillar αSyn in substantia nigra of σ1R(-/-) mice were age-dependently increased without the changes in αSyn monomers. The phosphorylation of αSyn monomers or oligomers in dopaminergic neurons was enhanced in σ1R(-/-) mice...
August 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28815595/sigma-1-receptor-ligands-inhibit-catecholamine-secretion-from-adrenal-chromaffin-cells-due-to-block-of-nicotinic-acetylcholine-receptors
#15
Rebecca L Brindley, Mary Beth Bauer, Nolan D Hartley, Kyle J Horning, Kevin P M Currie
Adrenal chromaffin cells (ACCs) are the neuroendocrine arm of the sympathetic nervous system and key mediators of the physiological stress response. Acetylcholine (ACh) released from preganglionic splanchnic nerves activates nicotinic acetylcholine receptors (nAChRs) on chromaffin cells causing membrane depolarization, opening voltage-gated Ca(2+) channels (VGCC), and exocytosis of catecholamines and neuropeptides. The serotonin transporter (SERT) is expressed in ACCs and interacts with 5-HT1A receptors to control secretion...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28792792/the-effect-of-rgd-ngr-peptide-modification-of-melanoma-differentiation-associated-gene-7-interleukin-24-on-its-receptor-attachment-an-in-silico-analysis
#16
Samaneh Bina, Seyed Younes Hosseini, Fatemeh Shenavar, Ebrahim Hosseini, Mojtaba Mortazavi
Melanoma differentiation-associated gene-7 (mda-7/interleukin [IL]-24), a unique tumor suppressor gene, induces selective apoptosis in tumor cells. Secreted IL-24 binds to heterodimeric receptor complexes of IL-20R1/IL-20R2, IL-22R1/IL-20R2, or sigma-1 receptor (Sig1R) that consequently enhances apoptosis. However, this mechanism is not well understood and most likely involves different pathways. Targeting of cytokine by tumor homing peptides (THPs) to the tumor cell surface molecule-like integrin shows to be beneficial in gene immunotherapy approaches...
August 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28791385/sigma-1-receptor-activation-ameliorates-anxiety-like-behavior-through-nr2a-creb-bdnf-signaling-pathway-in-a-rat-model-submitted-to-single-prolonged-stress
#17
Li-Li Ji, Jun-Bo Peng, Chang-Hai Fu, Lei Tong, Zhen-Yu Wang
Accumulating evidence has demonstrated that the σ-1 receptor (σ‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that σ‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of σ‑1R in PTSD...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28767411/sigma-1-and-sigma-2-receptor-ligands-induce-apoptosis-and-autophagy-but-have-opposite-effect-on-cell-proliferation-in-uveal-melanoma
#18
Lucia Longhitano, Carlo Castruccio Castracani, Daniele Tibullo, Roberto Avola, Maria Viola, Giuliano Russo, Orazio Prezzavento, Agostino Marrazzo, Emanuele Amata, Michele Reibaldi, Antonio Longo, Andrea Russo, Nunziatina Laura Parrinello, Giovanni Li Volti
Uveal melanoma is the most common primary intraocular tumor in adults, with about 1200-1500 new cases occurring per year in the United States. Metastasis is a frequent occurrence in uveal melanoma, and outcomes are poor once distant spread occurs and no clinically significant chemotherapeutic protocol is so far available. The aim of the present study was to test the effect of various σ1 and σ2 receptor ligands as a possible pharmacological strategy for this rare tumor. Human uveal melanoma cells (92.1) were treated with various concentrations of different σ2 ligands (haloperidol and haloperidol metabolite II) and σ1 ligand ((+)-pentazocine) at various concentrations (1, 10 and 25 μM) and time points (0, 4 h, 8 h, 24 h and 48 h)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756263/synthesis-and-pharmacological-evaluation-of-benzamide-derivatives-as-potent-and-selective-sigma-1-protein-ligands
#19
Marion Donnier-Maréchal, Pascal Carato, Paul-Emmanuel Larchanché, Séverine Ravez, Rajaa Boulahjar, Amélie Barczyk, Bénédicte Oxombre, Patrick Vermersch, Patricia Melnyk
A series of novel benzamide-derived compounds was designed, synthesized and pharmacologically evaluated. Among all 37 synthesized compounds, two series were developed with the modulation of the nature, the position of atoms or groups on the benzamide scaffold, but also the nature of the amine group separated from the benzamide with 2, 3 or 4 methylene groups. In vitro competition binding assays against sigma proteins (sigma-1 S1R and sigma-2 S2R) revealed that most of them conferred S2R/S1R selectivity toward without cytotoxic effects on SY5Y cells, especially with the first series with compounds 7a-z...
July 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28756230/haloperidol-a-sigma-receptor-1-antagonist-promotes-ferroptosis-in-hepatocellular-carcinoma-cells
#20
Tao Bai, Shuai Wang, Yipu Zhao, Rongtao Zhu, Weijie Wang, Yuling Sun
Ferroptosis is a novel form of cell death, which is characterized by accumulation of reactive oxygen species (ROS). Sigma 1 receptor (S1R) has been suggested to function in oxidative stress metabolism. Both erastin and sorafenib significantly induced S1R protein expression. Haloperidol strongly promoted erastin- and sorafenib-induced cell death, which was blocked by ferrostatin-1 but not ZVAD-FMK or necrosulfonamide. During ferroptosis, haloperidol substantially increased the cellular levels of Fe(2+), GSH and lipid peroxidation...
July 26, 2017: Biochemical and Biophysical Research Communications
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