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https://www.readbyqxmd.com/read/28548278/neuropeptide-s-precursor-knockout-mice-display-memory-and-arousal-deficits
#1
Xiaobin Liu, Wei Si, Celia Garau, Kay Jüngling, Hans-Christian Pape, Stefan Schulz, Rainer K Reinscheid
Activation of Neuropeptide S (NPS) signaling has been found to produce arousal, wakefulness, anxiolytic-like behaviors and enhanced memory formation. In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells. NPS(-/-) mice were viable, fertile, and anatomically normal, when compared to their wildtype and heterozygous littermates. The total number of NPS neurons - although no longer synthesizing the peptide - was not affected by the knockout, as analyzed in NPS(-/-) /NPS(EGFP) double-transgenic mice...
May 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28542603/a-conformational-switch-high-throughput-screening-assay-and-allosteric-inhibition-of-the-flavivirus-ns2b-ns3-protease
#2
Matthew Brecher, Zhong Li, Binbin Liu, Jing Zhang, Cheri A Koetzner, Adham Alifarag, Susan A Jones, Qishan Lin, Laura D Kramer, Hongmin Li
The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors...
May 25, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28537485/a-nad-parp1-sirt1-axis-in-aging
#3
Andrew R Mendelsohn, James Larrick
NAD+ levels decline with age in diverse animals from C. elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors NR or NMN improves mitochondrial function and muscle, neural and melanocyte stem cell function in mice as well as increasing murine lifespan. Decreased NAD+ levels with age reduces SIRT1 function and reduces the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DCB1 to form a complex with PARP1, inhibiting PARP catalytic activity...
May 24, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28535906/the-effects-of-curcumin-on-proliferation-apoptosis-invasion-and-nedd4-expression-in-pancreatic-cancer
#4
Jingna Su, Xiuxia Zhou, Xuyuan Yin, Lixia Wang, Zhe Zhao, Yingying Hou, Nana Zheng, Jun Xia, Zhiwei Wang
Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers...
May 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28533935/a-review-of-the-emerging-potential-therapy-for-neurological-disorders-human-embryonic-stem-cell-therapy
#5
REVIEW
Geeta Shroff, Jyoti Dhanda Titus, Rhea Shroff
The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson's disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders...
2017: American Journal of Stem Cells
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#6
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528122/probdnf-inhibits-proliferation-migration-and-differentiation-of-mouse-neural-stem-cells
#7
Jia-Yi Li, Jia Liu, Nimshitha Pavathuparambil Abdul Manaph, Larisa Bobrovskaya, Xin-Fu Zhou
ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro...
May 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#8
Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523560/stem-cell-technology-for-epi-genetic-brain-disorders
#9
Renzo J M Riemens, Edilene S Soares, Manel Esteller, Raul Delgado-Morales
Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28518115/analysis-of-retinoic-acid-induced-neural-differentiation-of-mouse-embryonic-stem-cells-in-two-and-three-dimensional-embryoid-bodies
#10
Junning Yang, Chuanshen Wu, Ioana Stefanescu, Arie Horowitz
Mouse embryonic stem cells (ESCs) isolated from the inner mass of the blastocyst (typically at day E3.5), can be used as in vitro model system for studying early embryonic development. In the absence of leukemia inhibitory factor (LIF), ESCs differentiate by default into neural precursor cells. They can be amassed into a three dimensional (3D) spherical aggregate termed embryoid body (EB) due to its similarity to the early stage embryo. EBs can be seeded on fibronectin-coated coverslips, where they expand by growing two dimensional (2D) extensions, or implanted in 3D collagen matrices where they continue growing as spheroids, and differentiate into the three germ layers: endodermal, mesodermal, and ectodermal...
April 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516108/what-is-car-doing-in-the-middle-of-the-adult-neurogenic-road
#11
COMMENT
Sara Salinas, Felix Junyent, Nathalie Coré, Harold Cremer, Eric J Kremer
The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28508575/upregulation-of-inflammatory-mediators-in-the-ventricular-zone-after-cortical-stroke
#12
Adrianna N Gunton, Juan C Sanchez-Arias, Esther O Carmona-Wagner, Leigh E Wicki-Stordeur, Leigh Anne Swayne
PURPOSE: After cortical stroke, neural precursor cells (NPCs) in the distal ventricular zone (VZ) proliferate more rapidly and migrate towards the injured cortex. While evidence suggests this can enhance stroke recovery, the underlying molecular mechanisms initiating the response are poorly understood. Here we identified changes in protein expression in the ipsilateral VZ early (4 hours) after stroke to gain insight into the initial mechanisms involved in NPC activation post-stroke. EXPERIMENTAL DESIGN: Four hours after photothrombotic stroke (or sham surgery control) in the sensorimotor cortex, adult mice (10 stroke, 10 sham) were subjected to cardiac perfusion with PBS, and ipsilateral and contralateral VZ tissue was microdissected...
May 15, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28500734/differentiation-of-human-olfactory-bulb-derived-neural-stem-cell-towards-oligodendrocyte-development
#13
H E Marei, Z Shouman, A Althani, N Afifi, A Abd-Elmaksoud, S Lashen, A Hasan, T Caceci, R Rizzi, C Cenciarelli, P Casalbore
In the central nervous system, oligodendrocytes are the glial element in charge of myelin formation. Obtaining an overall presence of oligodendrocyte precursor cells/oligodendrocytes. (OPCs/OLs) in culture from different sources of NSCs is an important research area, because OPCs/OLs may provide a promising therapeutic strategy for diseases affecting myelination of axons. The present study was designed to differentiate human olfactory bulb NSCs (OBNSCs) into OPCs/OLs and using expression profiling (RT-qPCR) gene, immunocytochemistry and specific protein expression to highlight molecular mechanism(s) underlying differentiation of human OBNSCs into OPCs/OLs...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498721/mechanisms-of-deubiquitinase-specificity-and-regulation
#14
Tycho E T Mevissen, David Komander
Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitinrelated modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8)...
May 12, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28493916/vesicular-glutamate-transporters-play-a-role-in-neuronal-differentiation-of-cultured-svz-derived-neural-precursor-cells
#15
Eduardo H Sánchez-Mendoza, Victor Bellver-Landete, Carmen Arce, Thorsten R Doeppner, Dirk M Hermann, María Jesús Oset-Gasque
The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes...
2017: PloS One
https://www.readbyqxmd.com/read/28486630/paired-related-homeobox-1-transactivates-dopamine-d2-receptor-to-maintain-propagation-and-tumorigenicity-of-glioma-initiating-cells
#16
Yamu Li, Wen Wang, Fangyu Wang, Qiushuang Wu, Wei Li, Xiaoling Zhong, Kuan Tian, Tao Zeng, Liang Gao, Ying Liu, Shu Li, Xiaobing Jiang, Guangwei Du, Yan Zhou
Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 (PRRX1), a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation...
May 9, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28475175/nucleosome-eviction-along-with-h3k9ac-deposition-enhances-sox2-binding-during-human-neuroectodermal-commitment
#17
Yanhua Du, Zhenping Liu, Xinkai Cao, Xiaolong Chen, Zhenyu Chen, Xiaobai Zhang, Xiaoqing Zhang, Cizhong Jiang
Neuroectoderm is an important neural precursor. However, chromatin remodeling and its epigenetic regulatory roles during the differentiation of human neuroectodermal cells (hNECs) from human embryonic stem cells (hESCs) remain largely unexplored. Here, we obtained hNECs through directed differentiation from hESCs, and determined chromatin states in the two cell types. Upon differentiation, H2A.Z-mediated nucleosome depletion leads to an open chromatin structure in promoters and upregulates expression of neuroectodermal genes...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28464358/mir-1297-regulates-neural-stem-cell-differentiation-and-viability-through-controlling-hes1-expression
#18
Jiaolin Zheng, Dan Yi, Xiaodong Shi, Huaizhang Shi
OBJECTIVES: Neural stem cells (NSCs) are self-renewing, undifferentiated and multipotent precursors that can generate neuronal and glial lineages. MicroRNAs (miRNAs) are small non-coding RNAs that act crucial roles in cell proliferation, differentiation and migration. However, the role of miR-1297 in the development of NSCs is still unknown. MATERIALS AND METHODS: Primary NSCs were isolated from rat's embryos. The expression of miR-1297 and Hes1 were measured by qRT-PCR...
May 2, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28461069/characterization-of-the-zika-virus-two-component-ns2b-ns3-protease-and-structure-assisted-identification-of-allosteric-small-molecule-antagonists
#19
Sergey A Shiryaev, Chen Farhy, Antonella Pinto, Chun-Teng Huang, Nicole Simonetti, Annie Elong Ngono, Antimone Dewing, Sujan Shresta, Anthony B Pinkerton, Piotr Cieplak, Alex Y Strongin, Alexey V Terskikh
The recent re-emergence of Zika virus (ZIKV)(1), a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents...
April 29, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28453954/local-delivery-of-chondroitinase-abc-with-or-without-stromal-cell-derived-factor-1%C3%AE-promotes-functional-repair-in-the-injured-rat-spinal-cord
#20
Malgosia M Pakulska, Charles H Tator, Molly S Shoichet
Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradation of the glial scar, using chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells (NPCs), using stromal cell-derived factor 1α (SDF)...
July 2017: Biomaterials
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