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Boris Ferger - One of the best experts on this subject based on the ideXlab platform.
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site specific action of l 3 4 dihydroxyphenylalanine in the striatum but not globus pallidus and substantia nigra pars reticulata evokes dyskinetic movements in chronic l 3 4 dihydroxyphenylalanine treated 6 hydroxyDopamine lesioned rats
Neuroscience, 2010Co-Authors: Kerstin Buck, Patrizia Voehringer, Boris FergerAbstract:Abstract Dyskinesia eventually develops in the majority of Parkinson's disease patients treated with l -3,4-dihydroxyphenylalanine ( l -Dopa). We have investigated the effect of an acute and local administration of l -Dopa, GABA and glutamate to provoke dyskinetic movements in three basal ganglia structures (striatum, globus pallidus (GP) and substantia nigra pars reticulata (SNr)) of chronically l -Dopa-treated, unilaterally 6-hydroxyDopamine-lesioned rats. We demonstrated that l -Dopa administration into the lesioned striatum using the technique of reverse in vivo microdialysis was an effective trigger to switch on dyskinesia. Notably, local l -Dopa perfusion at the same concentration in the ipsilateral GP and SNr did not provoke significant dyskinetic behaviour. Neither GABA nor glutamate triggered dyskinetic movements in the striatum, GP or SNr. We postulate a site-specific action of l -Dopa for the evocation of already established dyskinesia since l -Dopa in the striatum but not in the GP or SNr switched on dyskinetic behaviour.
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the α2 adrenoceptor antagonist idazoxan alleviates l Dopa induced dyskinesia by reduction of striatal Dopamine levels an in vivo microdialysis study in 6 hydroxyDopamine lesioned rats
Journal of Neurochemistry, 2010Co-Authors: Kerstin Buck, Patrizia Voehringer, Boris FergerAbstract:l-Dopa-induced dyskinesia is characterised by debilitating involuntary movement, which limits quality of life in patients suffering from Parkinson’s disease. Here, we investigate effects of the α2 adrenoceptor antagonist idazoxan on l-Dopa-induced dyskinesia as well as on alterations of extracellular l-Dopa and Dopamine (DA) levels in the striatum in dyskinetic rats. Male Wistar rats were unilaterally lesioned with 6-hydroxyDopamine and subsequently treated with l-Dopa/benserazide to induce stable dyskinetic movements. Administration of idazoxan [(9 mg/kg, intraperitoneal (i.p.)] significantly alleviated l-Dopa-induced dyskinesia, whereas idazoxan (3 mg/kg, i.p.) did not affect dyskinetic behaviour. Bilateral in vivo microdialysis revealed that idazoxan 9 mg/kg reduces extracellular peak l-Dopa levels in the lesioned and intact striatum as well as DA levels in the lesioned striatum. In parallel, the exposure to idazoxan in the striatum was monitored. Furthermore, no idazoxan and l-Dopa drug–drug interaction was found in plasma, brain tissue and CSF. In conclusion, the decrease of l-Dopa-derived extracellular DA levels in the lesioned striatum significantly contributes to the anti-dyskinetic effect of idazoxan.
Phillip B. Messersmith - One of the best experts on this subject based on the ideXlab platform.
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seamless metallic coating and surface adhesion of self assembled bioinspired nanostructures based on di 3 4 dihydroxy l phenylalanine peptide motif
ACS Nano, 2014Co-Authors: Galit Fichman, Phillip B. Messersmith, Lihi Adlerabramovich, Suresh Manohar, Iris Mironiharpaz, Tom Guterman, Dror Seliktar, Ehud GazitAbstract:The noncoded aromatic 3,4-dihydroxy-l-phenylalanine (Dopa) amino acid has a pivotal role in the remarkable adhesive properties displayed by marine mussels. These properties have inspired the design of adhesive chemical entities through various synthetic approaches. Dopa-containing bioinspired polymers have a broad functional appeal beyond adhesion due to the diverse chemical interactions presented by the catechol moieties. Here, we harnessed the molecular self-assembly abilities of very short peptide motifs to develop analogous Dopa-containing supramolecular polymers. The Dopa-containing Dopa–Dopa and Fmoc–Dopa–Dopa building blocks were designed by substituting the phenylalanines in the well-studied diphenylalanine self-assembling motif and its 9-fluorenylmethoxycarbonyl (Fmoc)-protected derivative. These peptides self-organized into fibrillar nanoassemblies, displaying high density of catechol functional groups. Furthermore, the Fmoc–Dopa–Dopa peptide was found to act as a low molecular weight hydrogelat...
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convenient synthesis of acetonide protected 3 4 dihydroxyphenylalanine Dopa for fmoc solid phase peptide synthesis
Tetrahedron Letters, 2008Co-Authors: Zhongqiang Liu, Phillip B. MessersmithAbstract:We report a facile approach to the synthesis of acetonide and Fmoc-protected 3,4-dihydroxyphenylalanine (Dopa), Fmoc-Dopa(acetonide)-OH. By protecting the amino group of Dopa with a phthaloyl group and the carboxyl group as a methyl ester, acetonide protection of the catechol of Dopa derivative was realized in the presence of p-toluenesulfonic acid. Following removal of protecting groups, the intermediate was converted to Fmoc-Dopa(acetonide)-OH, which was successfully incorporated into a short Dopa-containing peptide, derived from marine tubeworm cement proteins Pc1 and Pc2.
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synthesis of 3 4 dihydroxyphenylalanine Dopa containing monomers and their co polymerization with peg diacrylate to form hydrogels
Journal of Biomaterials Science-polymer Edition, 2004Co-Authors: Bruce P Lee, Kui Huang, Nelson F Nunalee, Kenneth R Shull, Phillip B. MessersmithAbstract:L-3,4-Dihydroxyphenylalanine (Dopa) is an unusual amino acid found in mussel adhesive proteins (MAPs) that is believed to lend adhesive characteristics to these proteins. Most previous efforts to incorporate Dopa into hydrogels have utilized oxidative cross-linking, which is hypothesized to reduce the adhesive properties of Dopa and requires reagents that are harmful to biological tissues. In this paper, we describe the synthesis of N-methacrylated Dopa monomers and their copolymerization with poly(ethylene glycol) diacrylate (PEG-DA) using either ultraviolet (UV) or visible light. The effect of Dopa containing monomers on gelation time, gel conversion and elastic modulus of the photocured hydrogels was investigated. Despite a retarding effect of Dopa on photopolymerization, Dopa was successfully incorporated into hydrogels with elastic moduli suitable for many biomedical applications. The incorporation of Dopa into hydrogels by photopolymerization may lead to new adhesive hydrogels for medical applications.
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synthesis and gelation of Dopa modified poly ethylene glycol hydrogels
Biomacromolecules, 2002Co-Authors: Jeffrey L. Dalsin, Phillip B. MessersmithAbstract:3,4-Dihydroxyphenylalanine (Dopa) residues are known for their ability to impart adhesive and curing properties to mussel adhesive proteins. In this paper, we report the preparation of linear and branched Dopa-modified poly(ethylene glycol)s (PEG-Dopas) containing one to four Dopa endgroups. Gel permeation chromatography−multiple-angle laser light scattering analysis of methoxy-PEG-Dopa in the presence of oxidizing reagents (sodium periodate, horseradish peroxidase, and mushroom tyrosinase) revealed the formation of oligomers of methoxy-PEG-Dopa, presumably resulting from oxidative polymerization of Dopa endgroups. In the case of PEG-Dopas containing two or more Dopa endgroups, oxidative polymerization resulted in polymer network formation and rapid gelation. The amount of time required for gelation of aqueous PEG-Dopa solutions was found to be as little as 1 min and was dependent on the polymer architecture as well as the type and concentration of oxidizing reagent used. Analysis of reaction mixtures by ...
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synthesis and gelation of Dopa modified poly ethylene glycol hydrogels
Biomacromolecules, 2002Co-Authors: Bruce P Lee, Jeffrey L. Dalsin, Phillip B. MessersmithAbstract:3,4-Dihydroxyphenylalanine (Dopa) residues are known for their ability to impart adhesive and curing properties to mussel adhesive proteins. In this paper, we report the preparation of linear and branched Dopa-modified poly(ethylene glycol)s (PEG-Dopas) containing one to four Dopa endgroups. Gel permeation chromatography-multiple-angle laser light scattering analysis of methoxy-PEG-Dopa in the presence of oxidizing reagents (sodium periodate, horseradish peroxidase, and mushroom tyrosinase) revealed the formation of oligomers of methoxy-PEG-Dopa, presumably resulting from oxidative polymerization of Dopa endgroups. In the case of PEG-Dopas containing two or more Dopa endgroups, oxidative polymerization resulted in polymer network formation and rapid gelation. The amount of time required for gelation of aqueous PEG-Dopa solutions was found to be as little as 1 min and was dependent on the polymer architecture as well as the type and concentration of oxidizing reagent used. Analysis of reaction mixtures by UV-vis spectroscopy allowed the identification of reaction intermediates and the elucidation of reaction pathways. On the basis of the observed reaction intermediates, oxidation of the catechol side chain of Dopa resulted in the formation of highly reactive Dopa-quinone, which further reacted to form cross-linked products via one of several pathways, depending on the presence or absence of N-terminal protecting groups on the PEG-Dopa. N-Boc protected PEG-Dopa cross-linked via phenol coupling and quinone methide tanning pathways, whereas PEG-Dopa containing a free amino group cross-linked via a pathway that resembled melanogenesis. Similar differences were observed for the rate of gel formation as well as the molecular weight between cross-links ((-)M(c)), calculated using equilibrium swelling and the Flory-Rehner equation.
Kerstin Buck - One of the best experts on this subject based on the ideXlab platform.
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site specific action of l 3 4 dihydroxyphenylalanine in the striatum but not globus pallidus and substantia nigra pars reticulata evokes dyskinetic movements in chronic l 3 4 dihydroxyphenylalanine treated 6 hydroxyDopamine lesioned rats
Neuroscience, 2010Co-Authors: Kerstin Buck, Patrizia Voehringer, Boris FergerAbstract:Abstract Dyskinesia eventually develops in the majority of Parkinson's disease patients treated with l -3,4-dihydroxyphenylalanine ( l -Dopa). We have investigated the effect of an acute and local administration of l -Dopa, GABA and glutamate to provoke dyskinetic movements in three basal ganglia structures (striatum, globus pallidus (GP) and substantia nigra pars reticulata (SNr)) of chronically l -Dopa-treated, unilaterally 6-hydroxyDopamine-lesioned rats. We demonstrated that l -Dopa administration into the lesioned striatum using the technique of reverse in vivo microdialysis was an effective trigger to switch on dyskinesia. Notably, local l -Dopa perfusion at the same concentration in the ipsilateral GP and SNr did not provoke significant dyskinetic behaviour. Neither GABA nor glutamate triggered dyskinetic movements in the striatum, GP or SNr. We postulate a site-specific action of l -Dopa for the evocation of already established dyskinesia since l -Dopa in the striatum but not in the GP or SNr switched on dyskinetic behaviour.
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the α2 adrenoceptor antagonist idazoxan alleviates l Dopa induced dyskinesia by reduction of striatal Dopamine levels an in vivo microdialysis study in 6 hydroxyDopamine lesioned rats
Journal of Neurochemistry, 2010Co-Authors: Kerstin Buck, Patrizia Voehringer, Boris FergerAbstract:l-Dopa-induced dyskinesia is characterised by debilitating involuntary movement, which limits quality of life in patients suffering from Parkinson’s disease. Here, we investigate effects of the α2 adrenoceptor antagonist idazoxan on l-Dopa-induced dyskinesia as well as on alterations of extracellular l-Dopa and Dopamine (DA) levels in the striatum in dyskinetic rats. Male Wistar rats were unilaterally lesioned with 6-hydroxyDopamine and subsequently treated with l-Dopa/benserazide to induce stable dyskinetic movements. Administration of idazoxan [(9 mg/kg, intraperitoneal (i.p.)] significantly alleviated l-Dopa-induced dyskinesia, whereas idazoxan (3 mg/kg, i.p.) did not affect dyskinetic behaviour. Bilateral in vivo microdialysis revealed that idazoxan 9 mg/kg reduces extracellular peak l-Dopa levels in the lesioned and intact striatum as well as DA levels in the lesioned striatum. In parallel, the exposure to idazoxan in the striatum was monitored. Furthermore, no idazoxan and l-Dopa drug–drug interaction was found in plasma, brain tissue and CSF. In conclusion, the decrease of l-Dopa-derived extracellular DA levels in the lesioned striatum significantly contributes to the anti-dyskinetic effect of idazoxan.
Xingguo Xiao - One of the best experts on this subject based on the ideXlab platform.
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cytosolic and nuclear co localization of betalain biosynthetic enzymes in tobacco suggests that betalains are synthesized in the cytoplasm and or nucleus of betalainic plant cells
Frontiers in Plant Science, 2017Co-Authors: Ning Chen, Zhihai Yu, Xingguo XiaoAbstract:Betalains replace anthocyanins as color pigments in most families of Caryophyllales. Unlike anthocyanins, betalains are derived from tyrosine via three enzymatic steps: hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-Dopa; step 1), and conversion of L-Dopa to betalamic acid (step 2), and to cyclo-Dopa (cDopa; step 3). The principal enzymes responsible for these reactions have been elucidated at the molecular level, but their subcellular localizations have not been explored; hence, the intracellular compartments wherein betalains are biosynthesized remain unknown. Here, we report on the subcellular localization of these principal enzymes. Bioinformatic predictors and N- and C-terminal GFP tagging in transgenic tobacco, showed that Beta vulgaris CYP76AD1 which mediates both step 1 and step 3, DODA1 that catalyzes step 2, and CYP76AD6 which also mediates step 1, were similarly localized to the cytoplasm and nucleus (although the P450s were also weakly present in the endoplasmic reticulum). These two compartments were also the principal locations of Mirabilis jalapa cDopa5GT. The cytoplasmic and nuclear co-localization of these key enzymes in tobacco suggests that betalains are biosynthesized in the cytoplasm and/or nucleus of betalain-containing plant cells. Elucidation of the subcellular compartmentation of betalain biosynthesis will facilitate the bioengineering of the betalain biosynthetic pathway in non-betalain-containing plants.
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Cytosolic and Nuclear Co-localization of Betalain Biosynthetic Enzymes in Tobacco Suggests that Betalains Are Synthesized in the Cytoplasm and/or Nucleus of Betalainic Plant Cells
Frontiers Media S.A., 2017Co-Authors: Ning Chen, Xingguo XiaoAbstract:Betalains replace anthocyanins as color pigments in most families of Caryophyllales. Unlike anthocyanins, betalains are derived from tyrosine via three enzymatic steps: hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-Dopa; step 1), and conversion of L-Dopa to betalamic acid (step 2), and to cyclo-Dopa (cDopa; step 3). The principal enzymes responsible for these reactions have been elucidated at the molecular level, but their subcellular localizations have not been explored; hence, the intracellular compartments wherein betalains are biosynthesized remain unknown. Here, we report on the subcellular localization of these principal enzymes. Bioinformatic predictors and N- and C-terminal GFP tagging in transgenic tobacco, showed that Beta vulgaris CYP76AD1 which mediates both steps 1 and 3, DODA1 that catalyzes step 2, and CYP76AD6 which also mediates step 1, were similarly localized to the cytoplasm and nucleus (although the P450s were also weakly present in the endoplasmic reticulum). These two compartments were also the principal locations of Mirabilis jalapa cDopa5GT. The cytoplasmic and nuclear co-localization of these key enzymes in tobacco suggests that betalains are biosynthesized in the cytoplasm and/or nucleus of betalain-containing plant cells. Elucidation of the subcellular compartmentation of betalain biosynthesis will facilitate the bioengineering of the betalain biosynthetic pathway in non-betalain-containing plants
Jeanjacques Soghomonian - One of the best experts on this subject based on the ideXlab platform.
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subchronic administration of l Dopa to adult rats with a unilateral 6 hydroxyDopamine lesion of Dopamine neurons results in a sensitization of enhanced gaba release in the substantia nigra pars reticulata
Brain Research, 2006Co-Authors: Noriko Yamamoto, Christopher R Pierce, Jeanjacques SoghomonianAbstract:L-Dopa is the most effective pharmacological agent used for the symptomatic treatment of Parkinson's disease but long-term L-Dopa treatment induces involuntary abnormal movements such as dyskinesias. The present study, using in vivo microdialysis, investigated the effects of a single or subchronic administration of L-Dopa to adult rats with a unilateral 6-OHDA lesion of Dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr). The results indicate that a challenge injection of L-Dopa (50 mg/kg, i.p.) significantly increases GABA levels in the SNr of rats treated with a daily repeated administration of L-Dopa (50 mg/kg, i.p.). Further statistical analysis between groups also showed that extracellular GABA levels were significantly higher in the subchronic L-Dopa group than in the group receiving only one injection of L-Dopa. These results show that the subchronic administration of L-Dopa results in a sensitization of enhanced extracellular GABA levels in the SNr.