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https://www.readbyqxmd.com/read/29204248/ginsenoside-rg1-ameliorates-behavioral-abnormalities-and-modulates-the-hippocampal-proteomic-change-in-triple-transgenic-mice-of-alzheimer-s-disease
#1
Lulin Nie, Junxia Xia, Honglian Li, Zaijun Zhang, Ying Yang, Xinfeng Huang, Zhendan He, Jianjun Liu, Xifei Yang
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, so far, there are no effective measures to prevent and cure this deadly condition. Ginsenoside Rg1 (Rg1) was shown to improve behavioral abnormalities in AD; however, the potential mechanisms remain unclear. In this study, we pretreated 7-month-old 3xTg-AD mice for 6 weeks with Rg1 and evaluated the effects of Rg1 on the behaviors and the protein expression of hippocampal tissues. The behavioral tests showed that Rg1 could improve the memory impairment and ameliorate the depression-like behaviors of 3xTg-AD mice...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29149906/forebrain-specific-conditional-silencing-of-staufen2-alters-synaptic-plasticity-learning-and-memory-in-rats
#2
Stefan M Berger, Iván Fernández-Lamo, Kai Schönig, Sandra M Fernández Moya, Janina Ehses, Rico Schieweck, Stefano Clementi, Thomas Enkel, Sascha Grothe, Oliver von Bohlen Und Halbach, Inmaculada Segura, José María Delgado-García, Agnès Gruart, Michael A Kiebler, Dusan Bartsch
BACKGROUND: Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo. RESULTS: To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons...
November 17, 2017: Genome Biology
https://www.readbyqxmd.com/read/29118371/genetic-association-analysis-of-microrna137-and-its-target-complex-1-with-schizophrenia-in-han-chinese
#3
Weihong Lu, Yi Zhang, Xinyu Fang, Weixing Fan, Wei Tang, Jun Cai, Lisheng Song, Chen Zhang
Recent genome-wide association studies (GWAS) have identified a strong association signal of microRNA137 host gene (MIR137) with schizophrenia. MIR137 dysfunction results in downregulation of presynaptic target gene complexin 1 (CPLX1) and impairs synaptic plasticity in the hippocampus. In this study, we aimed to investigate whether the variants of MIR137 and CPLX1 confer susceptibility to schizophrenia in Han Chinese. This study employed 736 patients with schizophrenia patients and 751 well-matched healthy subjects for genetic analysis, and genotyped 12 SNPs within MIR137 and CPLX1...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29110463/8-nitro-cgmp-attenuates-the-interaction-between-snare-complex-and-complexin-through-s-guanylation-of-snap-25
#4
Yusuke Kishimoto, Kohei Kunieda, Atsushi Kitamura, Yuki Kakihana, Takaaki Akaike, Hideshi Ihara
8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is the second messenger in nitric oxide/reactive oxygen species redox signaling. This molecule covalently binds to protein thiol groups, called S-guanylation, and exerts various biological functions. Recently, we have identified synaptosomal-associated protein 25 (SNAP-25) as a target of S-guanylation, and demonstrated that S-guanylation of SNAP25 enhanced SNARE complex formation. In this study, we have examined the effects of S-guanylation of SNAP-25 on the interaction between the soluble SNARE complex and complexin (cplx), which binds to the SNARE complex with a high affinity...
November 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29089437/transient-hypoxemia-chronically-disrupts-maturation-of-preterm-fetal-ovine-subplate-neuron-arborization-and-activity
#5
Evelyn McClendon, Daniel C Shaver, Kiera Degener-O'Brien, Xi Gong, Thuan Nguyen, Anna Hoerder-Suabedissen, Zoltán Molnár, Claudia Mohr, Ben D Richardson, David J Rossi, Stephen A Back
Preterm infants are at risk for a broad spectrum of neurobehavioral disabilities associated with diffuse disturbances in cortical growth and development. During brain development, subplate neurons (SPNs) are a largely transient population that serves a critical role to establish functional cortical circuits. By dynamically integrating into developing cortical circuits, they assist in consolidation of intracortical and extracortical circuits. Although SPNs reside in close proximity to cerebral white matter, which is particularly vulnerable to oxidative stress, the susceptibility of SPNs remains controversial...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29066949/regulation-of-exocytotic-fusion-pores-by-snare-protein-transmembrane-domains
#6
REVIEW
Zhenyong Wu, Sathish Thiyagarajan, Ben O'Shaughnessy, Erdem Karatekin
Calcium-triggered exocytotic release of neurotransmitters and hormones from neurons and neuroendocrine cells underlies neuronal communication, motor activity and endocrine functions. The core of the neuronal exocytotic machinery is composed of soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs). Formation of complexes between vesicle-attached v- and plasma-membrane anchored t-SNAREs in a highly regulated fashion brings the membranes into close apposition. Small, soluble proteins called Complexins (Cpx) and calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium concentrations, but trigger release upon calcium increase...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28887593/v-snare-function-in-chromaffin-cells
#7
REVIEW
Madhurima Dhara, Ralf Mohrmann, Dieter Bruns
Vesicle fusion is elementary for intracellular trafficking and release of signal molecules, thus providing the basis for diverse forms of intercellular communication like hormonal regulation or synaptic transmission. A detailed characterization of the mechanisms underlying exocytosis is key to understand how the nervous system integrates information and generates appropriate responses to stimuli. The machinery for vesicular release employs common molecular players in different model systems including neuronal and neuroendocrine cells, in particular members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein family, Sec1/Munc18-like proteins, and other accessory factors...
September 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28880148/reconciling-isothermal-titration-calorimetry-analyses-of-interactions-between-complexin-and-truncated-snare-complexes
#8
Eric A Prinslow, Chad A Brautigam, Josep Rizo
Neurotransmitter release depends on the SNARE complex formed by syntaxin-1, synaptobrevin and SNAP-25, as well as on complexins, which bind to the SNARE complex and play active and inhibitory roles. A crystal structure of a Complexin-I fragment bearing a so-called 'superclamp' mutation bound to a truncated SNARE complex lacking the C-terminus of the synaptobrevin SNARE motif (SNAREΔ60) suggested that an 'accessory' α-helix of Complexin-I inhibits release by inserting into the C-terminus of the SNARE complex...
September 7, 2017: ELife
https://www.readbyqxmd.com/read/28880147/correction-re-visiting-the-trans-insertion-model-for-complexin-clamping
#9
Shyam S Krishnakumar, Feng Li, Jeff Coleman, Curtis M Schauder, Daniel Kümmel, Frédéric Pincet, James E Rothman, Karin M Reinisch
No abstract text is available yet for this article.
September 7, 2017: ELife
https://www.readbyqxmd.com/read/28813412/the-primed-snare-complexin-synaptotagmin-complex-for-neuronal-exocytosis
#10
Qiangjun Zhou, Peng Zhou, Austin L Wang, Dick Wu, Minglei Zhao, Thomas C Südhof, Axel T Brunger
Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE-complexin-synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface...
August 24, 2017: Nature
https://www.readbyqxmd.com/read/28776026/reconstitution-of-calcium-mediated-exocytosis-of-dense-core-vesicles
#11
Alex J B Kreutzberger, Volker Kiessling, Binyong Liang, Patrick Seelheim, Shrutee Jakhanwal, Reinhard Jahn, J David Castle, Lukas K Tamm
Regulated exocytosis is a process by which neurotransmitters, hormones, and secretory proteins are released from the cell in response to elevated levels of calcium. In cells, secretory vesicles are targeted to the plasma membrane, where they dock, undergo priming, and then fuse with the plasma membrane in response to calcium. The specific roles of essential proteins and how calcium regulates progression through these sequential steps are currently incompletely resolved. We have used purified neuroendocrine dense-core vesicles and artificial membranes to reconstruct in vitro the serial events that mimic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-dependent membrane docking and fusion during exocytosis...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28772123/molecular-mechanisms-of-synaptic-vesicle-priming-by-munc13-and-munc18
#12
Ying Lai, Ucheor B Choi, Jeremy Leitz, Hong Jun Rhee, Choongku Lee, Bekir Altas, Minglei Zhao, Richard A Pfuetzner, Austin L Wang, Nils Brose, JeongSeop Rhee, Axel T Brunger
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca(2+)-triggered amplitude and achieves Ca(2+) sensitivity at near-physiological concentrations...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28739947/morphologies-of-synaptic-protein-membrane-fusion-interfaces
#13
Preeti Gipson, Yoshiyuki Fukuda, Radostin Danev, Ying Lai, Dong-Hua Chen, Wolfgang Baumeister, Axel T Brunger
Neurotransmitter release is orchestrated by synaptic proteins, such as SNAREs, synaptotagmin, and complexin, but the molecular mechanisms remain unclear. We visualized functionally active synaptic proteins reconstituted into proteoliposomes and their interactions in a native membrane environment by electron cryotomography with a Volta phase plate for improved resolvability. The images revealed individual synaptic proteins and synaptic protein complex densities at prefusion contact sites between membranes. We observed distinct morphologies of individual synaptic proteins and their complexes...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28608594/melatonin-ameliorates-anxiety-and-depression-like-behaviors-and-modulates-proteomic-changes-in-triple-transgenic-mice-of-alzheimer-s-disease
#14
Lulin Nie, Gang Wei, Shengming Peng, Zhongsen Qu, Ying Yang, Qian Yang, Xinfeng Huang, Jianjun Liu, Zhixiong Zhuang, Xifei Yang
Alzheimer's disease (AD) is a devastating neurodegenerative disease accompanied by neuropsychiatric symptoms, such as anxiety and depression. The levels of melatonin decrease in brains of AD patients. The potential effect of melatonin on anxiety and depression behaviors in AD and the underlying mechanisms remain unclear. In this study, we treated 10-month-old triple transgenic mice of AD (3xTg-AD) with melatonin (10 mg/kg body weight/day) for 1 month and explored the effects of melatonin on anxiety and depression-like behaviors in 3xTg-AD mice and the protein expression of hippocampal tissues...
June 13, 2017: BioFactors
https://www.readbyqxmd.com/read/28603484/evolutionary-divergence-of-the-c-terminal-domain-of-complexin-accounts-for-functional-disparities-between-vertebrate-and-invertebrate-complexins
#15
Rachel T Wragg, Daniel A Parisotto, Zhenlong Li, Mayu S Terakawa, David Snead, Ishani Basu, Harel Weinstein, David Eliezer, Jeremy S Dittman
Complexin is a critical presynaptic protein that regulates both spontaneous and calcium-triggered neurotransmitter release in all synapses. Although the SNARE-binding central helix of complexin is highly conserved and required for all known complexin functions, the remainder of the protein has profoundly diverged across the animal kingdom. Striking disparities in complexin inhibitory activity are observed between vertebrate and invertebrate complexins but little is known about the source of these differences or their relevance to the underlying mechanism of complexin regulation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28596722/unique-structural-features-of-membrane-bound-c-terminal-domain-motifs-modulate-complexin-inhibitory-function
#16
David Snead, Alex L Lai, Rachel T Wragg, Daniel A Parisotto, Trudy F Ramlall, Jeremy S Dittman, Jack H Freed, David Eliezer
Complexin is a small soluble presynaptic protein that interacts with neuronal SNARE proteins in order to regulate synaptic vesicle exocytosis. While the SNARE-binding central helix of complexin is required for both the inhibition of spontaneous fusion and the facilitation of synchronous fusion, the disordered C-terminal domain (CTD) of complexin is specifically required for its inhibitory function. The CTD of worm complexin binds to membranes via two distinct motifs, one of which undergoes a membrane curvature dependent structural transition that is required for efficient inhibition of neurotransmitter release, but the conformations of the membrane-bound motifs remain poorly characterized...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28488209/mir-135a-regulates-synaptic-transmission-and-anxiety-like-behavior-in-amygdala
#17
Cecilia Mannironi, Antonio Biundo, Samyutha Rajendran, Francesca De Vito, Luana Saba, Silvia Caioli, Cristina Zona, Teresa Ciotti, Silvana Caristi, Emerald Perlas, Giorgia Del Vecchio, Irene Bozzoni, Arianna Rinaldi, Andrea Mele, Carlo Presutti
MicroRNAs are a class of non-coding RNAs with a growing relevance in the regulation of gene expression related to brain function and plasticity. They have the potential to orchestrate complex phenomena, such as the neuronal response to homeostatic challenges. We previously demonstrated the involvement of miR-135a in the regulation of early stress response. In the present study, we examine the role of miR-135a in stress-related behavior. We show that the knockdown (KD) of miR-135a in the mouse amygdala induces an increase in anxiety-like behavior...
May 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28456331/complexin-binding-to-membranes-and-acceptor-t-snares-explains-its-clamping-effect-on-fusion
#18
Rafal Zdanowicz, Alex Kreutzberger, Binyong Liang, Volker Kiessling, Lukas K Tamm, David S Cafiso
Complexin-1 is a SNARE effector protein that decreases spontaneous neurotransmitter release and enhances evoked release. Complexin binds to the fully assembled four-helical neuronal SNARE core complex as revealed in competing molecular models derived from x-ray crystallography. Presently, it is unclear how complexin binding to the postfusion complex accounts for its effects upon spontaneous and evoked release in vivo. Using a combination of spectroscopic and imaging methods, we characterize in molecular detail how complexin binds to the 1:1 plasma membrane t-SNARE complex of syntaxin-1a and SNAP-25 while simultaneously binding the lipid bilayer at both its N- and C-terminal ends...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28422131/variants-in-cplx1-in-two-families-with-autosomal-recessive-severe-infantile-myoclonic-epilepsy-and-id
#19
Silke Redler, Tim M Strom, Thomas Wieland, Kirsten Cremer, Hartmut Engels, Felix Distelmaier, Jörg Schaper, Alma Küchler, Johannes R Lemke, Stephanie Jeschke, Nicole Schreyer, Heinrich Sticht, Margarete Koch, Hermann-Josef Lüdecke, Dagmar Wieczorek
For a large number of individuals with intellectual disability (ID), the molecular basis of the disorder is still unknown. However, whole-exome sequencing (WES) is providing more and more insights into the genetic landscape of ID. In the present study, we performed trio-based WES in 311 patients with unsolved ID and additional clinical features, and identified homozygous CPLX1 variants in three patients with ID from two unrelated families. All displayed marked developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar cleft in addition...
June 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28392696/compound-porcine-cerebroside-and-ganglioside-injection-attenuates-cerebral-ischemia-reperfusion-injury-in-rats-by-targeting-multiple-cellular-processes
#20
Mingyang Wang, Yi Zhang, Lu Feng, Ji Zheng, Shujie Fan, Junya Liu, Nan Yang, Yanyong Liu, Pingping Zuo
BACKGROUND: Compound porcine cerebroside and ganglioside injection (CPCGI) is a neurotrophic drug used clinically to treat certain functional disorders of brain. Despite its extensive usage throughout China, the exact mechanistic targets of CPCGI are unknown. This study was carried out to investigate the protective effect of CPCGI against ischemic neuronal damage in rats with middle cerebral artery occlusion (MCAO) reperfusion injury and to investigate the neuroprotective mechanisms of CPCGI...
2017: Neuropsychiatric Disease and Treatment
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