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Sigma receptor

Ying Bai, Yuan Zhang, Jun Hua, Xiangyu Yang, Xiaotian Zhang, Ming Duan, Xinjian Zhu, Wenhui Huang, Jie Chao, Rongbin Zhou, Gang Hu, Honghong Yao
MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs)...
October 21, 2016: Scientific Reports
A Eraso-Pichot, R Larramona-Arcas, E Vicario-Orri, R Villalonga, L Pardo, E Galea, R Masgrau
Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1...
October 19, 2016: Cellular and Molecular Life Sciences: CMLS
Susan Z Lever, Kuo-Hsien Fan, John R Lever
INTRODUCTION: Aspects of radiopharmaceutical development are illustrated through preclinical studies of [(125)I]-(E)-1-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-4-(iodoallyl)piperazine ([(125)I]-E-IA-BF-PE-PIPZE), a radioligand for sigma-1 (σ1) receptors, coupled with examples from the recent literature. Findings are compared to those previously observed for [(125)I]-(E)-1-(2-(2,3-dimethoxy-5-yl)ethyl)-4-(iodoallyl)piperazine ([(125)I]-E-IA-DM-PE-PIPZE). METHODS: Syntheses of E-IA-BF-PE-PIPZE and [(125)I]-E-IA-BF-PE-PIPZE were accomplished by standard methods...
September 3, 2016: Nuclear Medicine and Biology
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
Minhan Ka, Yeon-Hee Kook, Ke Liao, Shilpa Buch, Woo-Yang Kim
Cocaine is a highly addictive narcotic associated with dendritic spine plasticity in the striatum. However, it remains elusive whether cocaine modifies spines in a cell type-specific or region-specific manner or whether it alters different types of synapses in the brain. In addition, there is a paucity of data on the regulatory mechanism(s) involved in cocaine-induced modification of spine density. In the current study, we report that cocaine exposure differentially alters spine density, spine morphology, and the types of synapses in hippocampal and cortical neurons...
October 13, 2016: Cell Death & Disease
Trent Conroy, Madhura Manohar, Yu Gong, Shane M Wilkinson, Michael Webster, Brian P Lieberman, Samuel D Banister, Tristan A Reekie, Robert H Mach, Louis M Rendina, Michael Kassiou
The sigma-1 receptor (S1R) has attracted a great deal of attention as a prospective drug target due to its involvement in numerous neurological disorders and, more recently, for its therapeutic potential in neuropathic pain. As there was no crystal structure of this membrane-bound protein reported until 2016, ligand generation was driven by pharmacophore refinements to the general model suggested by Glennon and co-workers. The generalised S1R pharmacophore comprises a central region where a basic amino group is preferred, flanked by two hydrophobic groups...
October 4, 2016: Organic & Biomolecular Chemistry
Yusuke Naito, Alfred Kihoon Lee, Hideto Takahashi
Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ)...
September 30, 2016: Neuroscience Research
Attila Szabo, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, Ede Frecska
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins...
2016: Frontiers in Neuroscience
Mika Naganawa, Shu-Fei Lin, Keunpoong Lim, David Labaree, Jim Ropchan, Paul Harris, Yiyun Huang, Masanori Ichise, Richard E Carson, Gary W Cline
INTRODUCTION: (18)F-Fluoropropyl-(+)-dihydrotetrabenazine ((18)F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about (18)F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of (18)F-FP-(+)-DTBZ and its inactive enantiomer (18)F-FP-(-)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions...
September 2, 2016: Nuclear Medicine and Biology
Mikhail Paveliev, Keith K Fenrich, Mikhail Kislin, Juha Kuja-Panula, Evgeny Kulesskiy, Markku Varjosalo, Tommi Kajander, Ekaterina Mugantseva, Anni Ahonen-Bishopp, Leonard Khiroug, Natalia Kulesskaya, Geneviève Rougon, Heikki Rauvala
Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma)...
September 27, 2016: Scientific Reports
Lei Miao, Jay M Newby, C Michael Lin, Lu Zhang, Feifei Xu, William Y Kim, M Gregory Forest, Samuel K Lai, Matthew I Milowsky, Sara E Wobker, Leaf Huang
The binding site barrier (BSB) was originally proposed to describe the binding behavior of antibodies to cells peripheral to blood vessels, preventing their further penetration into the tumors. Yet, it is revisited herein to describe the intratumoral cellular disposition of nanoparticles (NPs). Specifically, the BSB limits NP diffusion and results in unintended internalization of NPs by stroma cells localized near blood vessels. This not only limits the therapeutic outcome, but also promotes adverse off-target effects...
September 24, 2016: ACS Nano
Min Fang, Pei Zhang, Yanxin Zhao, Aiping Jin, Xueyuan Liu
Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression...
2016: American Journal of Translational Research
Fadil M Hannan, Valerie N Babinsky, Rajesh V Thakker
The extracellular calcium (Ca(2+) o)-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca(2+) o concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca(2+) o homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH)...
October 2016: Journal of Molecular Endocrinology
Alejandro Horga, Pedro J Tomaselli, Michael A Gonzalez, Matilde Laurà, Francesco Muntoni, Adnan Y Manzur, Michael G Hanna, Julian C Blake, Henry Houlden, Stephan Züchner, Mary M Reilly
OBJECTIVE: To describe the genetic and clinical features of a simplex patient with distal hereditary motor neuropathy (dHMN) and lower limb spasticity (Silver-like syndrome) due to a mutation in the sigma nonopioid intracellular receptor-1 gene (SIGMAR1) and review the phenotypic spectrum of mutations in this gene. METHODS: We used whole-exome sequencing to investigate the proband. The variants of interest were investigated for segregation in the family using Sanger sequencing...
October 11, 2016: Neurology
Marta Rui, Annamaria Marra, Vittorio Pace, Markus Juza, Daniela Rossi, Simona Collina
The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here, we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All of the studied compounds have been prepared both in racemic and enantiomerically-pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marta Rui, Daniela Rossi, Annamaria Marra, Mayra Paolillo, Sergio Schinelli, Daniela Curti, Anna Tesei, Michela Cortesi, Alice Zamagni, Erik Laurini, Sabrina Pricl, Dirk Schepmann, Bernhard Wűnsch, Ernst Urban, Vittorio Pace, Simona Collina
In the early 2000s, the Sigma Receptor (SR) family was identified as potential "druggable" target in cancer treatment. Indeed, high density of SRs was found in breast, lung, and prostate cancer cells, supporting the idea that SRs could play a role in tumor growth and progression. Moreover, a link between the degree of SR expression and tumor aggressiveness has been postulated, justified by the presence of SRs in high metastatic-potential cancer cells. As a consequence, considerable efforts have been devoted to the development of small molecules endowed with good affinity towards the two SR subtypes (S1R and S2R) with potential anticancer activity...
August 31, 2016: European Journal of Medicinal Chemistry
Lukas Pfeifer, Keary M Engle, George W Pidgeon, Hazel A Sparkes, Amber L Thompson, John M Brown, Véronique Gouverneur
Hydrogen bonding with fluoride is a key interaction encountered when analyzing the mode of action of 5'-fluoro-5'-deoxyadenosine synthase, the only known enzyme capable of catalyzing the formation of a C-F bond from F(-). Further understanding of the effect of hydrogen bonding on the structure and reactivity of complexed fluoride is therefore important for catalysis and numerous other applications, such as anion supramolecular chemistry. Herein we disclose a detailed study examining the structure of 18 novel urea-fluoride complexes in the solid state, by X-ray and neutron diffraction, and in solution phase and explore the reactivity of these complexes as a fluoride source in SN2 chemistry...
October 4, 2016: Journal of the American Chemical Society
Jessica L Hastie, Kyle B Williams, Lindsey L Bohr, Jon C Houtman, Lokesh Gakhar, Craig D Ellermeier
σ factors provide RNA polymerase with promoter specificity in bacteria. Some σ factors require activation in order to interact with RNA polymerase and transcribe target genes. The Extra-Cytoplasmic Function (ECF) σ factor, σV, is encoded by several Gram-positive bacteria and is specifically activated by lysozyme. This activation requires the proteolytic destruction of the anti-σ factor RsiV via a process of regulated intramembrane proteolysis (RIP). In many cases proteases that cleave at site-1 are thought to directly sense a signal and initiate the RIP process...
September 2016: PLoS Genetics
Sheu-Ran Choi, Soon-Gu Kwon, Hoon-Seong Choi, Ho-Jae Han, Alvin James Beitz, Jang-Hern Lee
We recently demonstrated that activation of spinal sigma-1 receptors (Sig-1Rs) induces pain hypersensitivity via the activation of neuronal nitric oxide synthase (nNOS) and NADPH oxidase 2 (Nox2). However, the potential direct interaction between nNOS-derived nitric oxide (NO) and Nox2-derived reactive oxygen species (ROS) is poorly understood, particularly with respect to the potentiation of NMDA receptor activity in the spinal cord associated with the development of central sensitization. Thus, the main purpose of this study was to investigate whether Sig-1R-induced and nNOS-derived NO modulates spinal Nox2 activation leading to an increase in ROS production and ultimately to the potentiation of NMDA receptor activity and pain hypersensitivity...
September 7, 2016: Biological & Pharmaceutical Bulletin
Clara Herrera-Arozamena, Olaia Martí-Marí, Martín Estrada, Mario de la Fuente Revenga, María Isabel Rodríguez-Franco
The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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