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Friedemann T.,HanseMerkur Center for Traditional Chinese Medicine | Ying Y.,Tongji University | Wang W.,Tongji University | Kramer E.R.,Center for Molecular Neurobiology Hamburg | And 4 more authors.
American Journal of Chinese Medicine | Year: 2016

The rhizome of Coptis chinensis is commonly used in traditional Chinese medicine alone or in combination with other herbs to treat diseases characterized by causing oxidative stress including inflammatory diseases, diabetes mellitus and neurodegenerative diseases. In particular, there is emerging evidence that Coptis chinensis is effective in the treatment of neurodegenerative diseases associated with oxidative stress. Hence, the aim of this study was to investigate the neuroprotective effect of Coptis chinensis in vitro and in vivo using MPP(Formula presented.) and MPTP models of Parkinson’s disease. MPP(Formula presented.) treated human SH-SY5Y neuroblastoma cells were used as a cell model of Parkinson’s disease. A 24(Formula presented.)h pre-treatment of the cells with the watery extract of Coptis chinensis significantly increased cell viability, as well as the intracellular ATP concentration and attenuated apoptosis compared to the MPP(Formula presented.) control. Further experiments with the main alkaloids of Coptidis chinensis, berberine, coptisine, jaterorrhizine and palmatine revealed that berberine and coptisine were the main active compounds responsible for the observed neuroprotective effect. However, the full extract of Coptis chinensis was more effective than the tested single alkaloids. In the MPTP-induced animal model of Parkinson’s disease, Coptis chinensis dose-dependently improved motor functions and increased tyrosine hydroxylase-positive neurons in the substantia nigra compared to the MPTP control. Based on the results of this work, Coptis chinensis and its main alkaloids could be considered potential candidates for the development of new treatment options for Parkinson’s disease. © 2016 World Scientific Publishing Company Source

Dieni S.,Albert Ludwigs University of Freiburg | Matsumoto T.,University of Basel | Matsumoto T.,Hiroshima University | Dekkers M.,University of Basel | And 12 more authors.
Journal of Cell Biology | Year: 2012

Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex biological processes including memory retention, its extremely low levels in the mature central nervous system have greatly complicated attempts to reliably localize it. Using rigorous specificity controls, we found that antibodies reacting either with BDNF or its pro-peptide both stained large dense core vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both moieties were ~10-fold more abundant than pro-BDNF. The lack of postsynaptic localization was confirmed in Bassoon mutants, a seizure-prone mouse line exhibiting markedly elevated levels of BDNF. These findings challenge previous conclusions based on work with cultured neurons, which suggested activity-dependent dendritic synthesis and release of BDNF. They instead provide an ultrastructural basis for an anterograde mode of action of BDNF, contrasting with the long-established retrograde model derived from experiments with nerve growth factor in the peripheral nervous system. © 2012 Dieni et al. Source

Yang N.-Y.,Sanford Burnham Institute for Medical Research | Fernandez C.,Sanford Burnham Institute for Medical Research | Richter M.,Sanford Burnham Institute for Medical Research | Richter M.,Center for Molecular Neurobiology Hamburg | And 5 more authors.
Cellular Signalling | Year: 2011

Receptor tyrosine kinases of the Eph family play multiple roles in the physiological regulation of tissue homeostasis and in the pathogenesis of various diseases, including cancer. The EphA2 receptor is highly expressed in most cancer cell types, where it has disparate activities that are not well understood. It has been reported that interplay of EphA2 with oncogenic signaling pathways promotes cancer cell malignancy independently of ephrin ligand binding and receptor kinase activity. In contrast, stimulation of EphA2 signaling with ephrin-A ligands can suppress malignancy by inhibiting the Ras-MAP kinase pathway, integrin-mediated adhesion, and epithelial to mesenchymal transition. Here we show that ephrin-A1 ligand-dependent activation of EphA2 decreases the growth of PC3 prostate cancer cells and profoundly inhibits the Akt-mTORC1 pathway, which is hyperactivated due to loss of the PTEN tumor suppressor. Our results do not implicate changes in the activity of Akt upstream regulators (such as Ras family GTPases, PI3 kinase, integrins, or the Ship2 lipid phosphatase) in the observed loss of Akt T308 and S473 phosphorylation downstream of EphA2. Indeed, EphA2 can inhibit Akt phosphorylation induced by oncogenic mutations of not only PTEN but also PI3 kinase. Furthermore, it can decrease the hyperphosphorylation induced by constitutive membrane-targeting of Akt. Our data suggest a novel signaling mechanism whereby EphA2 inactivates the Akt-mTORC1 oncogenic pathway through Akt dephosphorylation mediated by a serine/threonine phosphatase. Ephrin-A1-induced Akt dephosphorylation was observed not only in PC3 prostate cancer cells but also in other cancer cell types. Thus, activation of EphA2 signaling represents a possible new avenue for anti-cancer therapies that exploit the remarkable ability of this receptor to counteract multiple oncogenic signaling pathways. © 2010 Elsevier Inc. Source

Koster J.-D.,University of Hamburg | Leggewie B.,University of Hamburg | Blechner C.,University of Hamburg | Brandt N.,University of Hamburg | And 5 more authors.
Cellular Signalling | Year: 2016

Long-lasting synaptic plasticity is often accompanied by morphological changes as well as formation and/or loss of dendritic spines. Since the spine cytoskeleton mainly consists of actin filaments, morphological changes are primarily controlled by actin binding proteins (ABPs). Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) is a neuron-specific, actin bundling protein concentrated at dendritic spines. Here, we demonstrate that ITPKA depletion in mice increases the number of hippocampal spine-synapses while reducing average spine length. By employing actin to ABP ratios similar to those occurring at post synaptic densities, in addition to cross-linking actin filaments, ITPKA strongly inhibits Arp2/3-complex induced actin filament branching by displacing the complex from F-actin. In summary, our data show that in vivo ITPKA negatively regulates formation and/or maintenance of synaptic contacts in the mammalian brain. On the molecular level this effect appears to result from the ITPKA-mediated inhibition of Arp2/3-complex F-actin branching activity. © 2015 Elsevier Inc. Source

Loktionov E.Y.,Moscow State Technical University | Mikhaylova M.G.,Center for Molecular Neurobiology Hamburg | Sitnikov D.S.,RAS Joint Institute for High Temperatures
Instruments and Experimental Techniques | Year: 2016

A calcium cell signaling system is one of the first, which were formed in the course of evolution of systems. The understanding of calcium binding–uncaging dynamics is crucial in studies of corresponding intracellular processes. By now, a great number of calcium-dependent processes have been investigated. However, works that fully consider these processes are absent. This is specified in many respects by the instrumental abilities. In this work, requirements for the experimental setup intended for comprehensive studies of calcium interaction dynamics are briefly formulated, its block diagram is described, and the results of test experiments are presented. © 2016, Pleiades Publishing, Inc. Source

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