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https://www.readbyqxmd.com/read/28324201/potential-roles-of-mitochondria-associated-er-membranes-mams-in-traumatic-brain-injury
#1
REVIEW
Dongdong Sun, Xin Chen, Gang Gu, Jianhao Wang, Jianning Zhang
The endoplasmic reticulum (ER) and mitochondria have both been shown to be critical in cellular homeostasis. The functions of the ER and mitochondria are independent but interrelated. These two organelles could form physical interactions, known as MAMs, to regulate physiological functions between ER and mitochondria to maintain Ca(2+), lipid, and metabolite exchange. Several proteins are located in MAMs, including RNA-dependent protein kinase (PKR)-like ER kinase, inositol 1,4,5-trisphosphate receptors, phosphofurin acidic cluster sorting protein-2 and sigma-1 receptor to ensure regulation...
March 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28320023/-update-opipramol
#2
Maximilian Gahr, Christoph Hiemke, Bernhard J Connemann
Opipramol was developed in the 1960s as an antidepressant and has chemical similarities with tricyclic antidepressants. Pharmacodynamic properties with absent reuptake inhibition of serotonin and noradrenaline and agonism at sigma receptors distinguish opipramol from tricyclics. Furthermore, antidepressive effects are smaller than the anxiolytic ones. The mechanism of action of opipramol is currently not sufficiently understood. Agonistic effects at sigma receptors have been linked with therapeutic effects...
March 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/28316027/validation-of-dopamine-receptor-drd1-and-drd2-antibodies-using-receptor-deficient-mice
#3
Tamara Stojanovic, Michaela Orlova, Fernando J Sialana, Harald Höger, Stanislav Stuchlik, Ivan Milenkovic, Jana Aradska, Gert Lubec
Dopamine receptors 1 and 2 (DRD1, DRD2) are essential for signaling in the brain for a multitude of brain functions. Previous work using several antibodies against these receptors is abundant but only the minority of antibodies used have been validated and, therefore, the results of these studies remain uncertain. Herein, antibodies against DRD1 (Merck Millipore AB1765P, Santa Cruz Biotechnology sc-14001, Sigma Aldrich D2944, Alomone Labs ADR-001) and DRD2 (Abcam ab21218, Merck Millipore AB5084P, Santa Cruz Biotechnology sc-5303) have been tested using western blotting and immunohistochemistry on mouse striatum (wild type and corresponding knock-out mice) and when specific, they were further evaluated on rat and human striatum...
March 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28315279/the-role-of-sigma-1-receptor-as-a-neuroprotective-target-in-glaucoma
#4
Barbara Mysona, Neil Kansara, Jing Zhao, Kathryn Bollinger
The role of sigma 1 receptor (S1R) in glaucoma is emerging as a promising field of study. Glaucoma is an optic neuropathy that shares common pathogenic mechanisms with other neurodegenerative diseases such as Alzheimer's and Parkinson's disease . S1R modulates multiple cellular functions associated with neurodegeneration . These include Ca(2+) ion homeostasis, endoplasmic reticulum (ER) and oxidative stress , survival signaling pathways, neurotrophin secretion, and glial activation. S1R may also have neurorestorative properties including enhancement of neuronal plasticity and neurite outgrowth...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315278/peeking-into-sigma-1-receptor-functions-through-the-retina
#5
Timur A Mavlyutov, Lian-Wang Guo
This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315277/the-role-of-sigma1r-in-mammalian-retina
#6
Jing Wang, Xuezhi Cui, Penny Roon, Alan Saul, Sylvia B Smith
This review article focuses on studies of Sigma 1 Receptor (Sigma1R) and retina . It provides a brief overview of the earliest pharmacological studies performed in the late 1990s that provided evidence of the presence of Sigma1R in various ocular tissues. It then describes work from a number of labs concerning the location of Sigma1R in several retinal cell types including ganglion, Müller glia , and photoreceptors . The role of Sigma1R ligands in retinal neuroprotection is emphasized. Early studies performed in vitro clearly showed that targeting Sigma1R could attenuate stress-induced retinal cell loss...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#7
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315275/sigma-1-receptor-in-motoneuron-disease
#8
Renzo Mancuso, Xavier Navarro
Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315273/stimulation-of-the-sigma-1-receptor-and-the-effects-on-neurogenesis-and-depressive-behaviors-in-mice
#9
Kohji Fukunaga, Shigeki Moriguchi
Sigma-1 receptor (Sig-1R) is molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to mitochondria. Recent studies show that Sig-1R stimulation antagonizes depressive-like behaviors in animal models, but molecular mechanisms underlying this effect remain unclear. Here, we focus on the effects of Sig-1R ligands on hippocampal neurogenesis and depressive-like behaviors. Sig-1R stimulation also enhances CaMKII /CaMKIV and protein kinase B (Akt) activities in hippocampus. Therefore, we discuss the fundamental roles of Sig-1R, CaMKII /CaMKIV and protein kinase B (Akt) signaling in amelioration of depressive-like behaviors following Sig-1R stimulation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315272/sigma-receptors-and-substance-use-disorders
#10
Valentina Sabino, Callum Hicks, Pietro Cottone
Thanks to advances in neuroscience, addiction is now recognized as a chronic brain disease with genetic, developmental, and cultural components. Drugs of abuse, including alcohol, are able to produce significant neuroplastic changes responsible for the profound disturbances shown by drug addicted individuals. The current lack of efficacious pharmacological treatments for substance use disorders has encouraged the search for novel and more effective pharmacotherapies. Growing evidence strongly suggests that Sigma Receptors are involved in the addictive and neurotoxic properties of abused drugs, including cocaine , methamphetamine , and alcohol...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315271/role-of-sigma-1-receptor-in-cocaine-abuse-and-neurodegenerative-disease
#11
Yu Cai, Lu Yang, Fang Niu, Ke Liao, Shilpa Buch
Sigma-1 receptors (Sig-1R) are recognized as a unique class of non-G protein-coupled intracellular protein. Sig-1R binds to its ligand such as cocaine , resulting in dissociation of Sig-1R from mitochondrion-associated ER membrane (MAM) to the endoplasmic reticulum (ER), plasma membrane, and nuclear membrane, regulating function of various proteins. Sig-1R has diverse roles in both physiological as well as in pathogenic processes. The disruption of Sig-1R pathways has been implicated as causative mechanism(s) in the development of both neurodegenerative disorders such as Alzheimer disease (AD ), Parkinson disease (PD ), amyotrophic lateral sclerosis (ALS ) and Huntington Disease (HD ) ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315270/sigma-1-receptor-agonists-and-their-clinical-implications-in-neuropsychiatric-disorders
#12
Yakup Albayrak, Kenji Hashimoto
Accumulating evidence suggests that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some selective serotonin reuptake inhibitors (SSRIs). Among the SSRIs, the order of affinity for sigma-1 receptors is as follows: fluvoxamine > sertraline > fluoxetine > escitalopram > citalopram > paroxetine. Some SSRIs (e.g., fluvoxamine, fluoxetine and escitalopram) and other drugs (donepezil , ifenprodil , dehydroepiandeterone (DHEA)) potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, and these effects could be antagonized by the selective sigma-1 receptor antagonist NE-100...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315269/sigma-1-receptors-and-neurodegenerative-diseases-towards-a-hypothesis-of-sigma-1-receptors-as-amplifiers-of-neurodegeneration-and-neuroprotection
#13
Linda Nguyen, Brandon P Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, Rae R Matsumoto
Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315268/sigma-1-receptor-antagonists-a-new-class-of-neuromodulatory-analgesics
#14
Cristina Sánchez-Fernández, José Manuel Entrena, José Manuel Baeyens, Enrique José Cobos
The sigma-1 receptor is a unique ligand-operated chaperone present in key areas for pain control, in both the peripheral and central nervous system. Sigma-1 receptors interact with a variety of protein targets to modify their function. These targets include several G-protein-coupled receptors such as the μ-opioid receptor, and ion channels such as the N-methyl-D-aspartate receptor (NMDAR). Sigma-1 antagonists modify the chaperoning activity of sigma-1 receptor by increasing opioid signaling and decreasing NMDAR responses, consequently enhancing opioid antinociception and decreasing the sensory hypersensitivity that characterizes pathological pain conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315267/pharmacological-modulation-of-the-sigma-1-receptor-and-the-treatment-of-pain
#15
Manuel Merlos, Javier Burgueño, Enrique Portillo-Salido, Carlos Ramón Plata-Salamán, José Miguel Vela
There is a critical need for new analgesics acting through new mechanisms of action, which could increase the efficacy with respect to existing therapies and reduce their unwanted effects. Current preclinical evidence supports the modulatory role of sigma-1 receptors (σ1R) in nociception, mainly based on the pain-attenuated phenotype of σ1R knockout mice and on the antinociceptive effect exerted by σ1R antagonists on pains of different etiologies. σ1R is highly expressed in different pain areas of the CNS and the periphery (particularly dorsal root ganglia), and interacts and modulates the functionality of different receptors and ion channels ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315266/sigma-1-receptors-fine-tune-the-neuronal-networks
#16
Shang-Yi Anne Tsai, Tsung-Ping Su
The endoplasmic reticular (ER) protein sigma-1 receptor (Sig-1R) has been implicated in CNS disorders including but not limited to neurodegenerative diseases, depression , amnesia, and substance abuse. Sig-1Rs are particularly enriched in the specific domain where ER membranes make contacts with the mitochondria (MAM). Within that specific domain, Sig-1Rs play significant roles governing calcium signaling and reactive oxygen species homeostasis to maintain proper neuronal functions. Studies showed that the Sig-1R is pivotal to regulate neuroplasticity and neural survival via multiple aspects of mechanism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315265/sigma-1-receptor-and-ion-channel-dynamics-in-cancer
#17
Olivier Soriani, Raphaël Rapetti-Mauss
SigmaR1 is a multitasking chaperone protein which has mainly been studied in CNS physiological and pathophysiological processes such as pain, memory, neurodegenerative diseases (amyotrophic lateral sclerosis , Parkinson's and Alzheimer's diseases, retinal neurodegeneration ), stroke and addiction . Strikingly, G-protein and ion channels are the main client protein fami lies of this atypical chaperone and the recent advances that have been performed for the last 10 years demonstrate that SigmaR1 is principally activated following tissue injury and disease development to promote cell survival...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315264/the-evolution-of-the-sigma-2-%C3%AF-2-receptor-from-obscure-binding-site-to-bona-fide-therapeutic-target
#18
Chenbo Zeng, Robert H Mach
The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315262/a-review-of-the-human-sigma-1-receptor-structure
#19
Felipe Ossa, Jason R Schnell, José Luis Ortega-Roldan
The Sigma-1 Receptor (S1R) is a small, ligand-regulated integral membrane protein involved in cell homeostasis and the cellular stress response. The receptor has a multitude of protein and small molecule interaction partners with therapeutic potential. Newly reported structures of the human S1R in ligand-bound states provides essential insights into small molecule binding in the context of the overall protein structure. The structure also raises many interesting questions and provides an excellent starting point for understanding the molecular tricks employed by this small membrane receptor to modulate a large number of signaling events...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315261/structural-perspectives-on-sigma-1-receptor-function
#20
Assaf Alon, Hayden Schmidt, Sanduo Zheng, Andrew C Kruse
The sigma-1 receptor is an enigmatic ER-resident transmembrane protein linked to a variety of human diseases. Although the receptor was first cloned 20 years ago, the molecular structure of the protein and the mechanistic basis for its interaction with drug-like small molecules have remained unclear until recently. The determination of the first crystal structure of human sigma-1 offered the first detailed views of the sigma-1 architecture, and revealed an unusual overall fold with a single transmembrane helix in each protomer...
2017: Advances in Experimental Medicine and Biology
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