Prukop, Thomas

[["dc.bibliographiccitation.journal","Annals of Clinical and Translational Neurology"],["dc.contributor.author","Epplen, Dirk B."],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Nientiedt, Tobias"],["dc.contributor.author","Albrecht, Philipp"],["dc.contributor.author","Arlt, Friederike A."],["dc.contributor.author","Stassart, Ruth M."],["dc.contributor.author","Kassmann, Celia M."],["dc.contributor.author","Methner, Axel"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Sereda, Michael W."],["dc.date.accessioned","2019-07-09T11:41:24Z"],["dc.date.available","2019-07-09T11:41:24Z"],["dc.date.issued","2015"],["dc.description.abstract","Objective: Pelizaeus–Merzbacher disease (PMD) is a progressive and lethal leukodystrophy caused by mutations affecting the proteolipid protein (PLP1) gene. The most common cause of PMD is a duplication of PLP1 and at present there is no curative therapy available. Methods: By using transgenic mice carrying additional copies of Plp1, we investigated whether curcumin diet ameliorates PMD symptoms. The diet of Plp1 transgenic mice was supplemented with curcumin for 10 consecutive weeks followed by phenotypical, histological and immunohistochemical analyses of the central nervous system. Plp1 transgenic and wild-type mice fed with normal chow served as controls. Results: Curcumin improved the motor phenotype performance of Plp1 transgenic mice by 50% toward wild-type level and preserved myelinated axons by 35% when compared to Plp1 transgenic controls. Furthermore, curcumin reduced astrocytosis, microgliosis and lymphocyte infiltration in Plp1 transgenic mice. Curcumin diet did not affect the pathologically increased Plp1 mRNA abundance. However, high glutathione levels indicating an oxidative misbalance in the white matter of Plp1 transgenic mice were restored by curcumin treatment. Interpretation: Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication. ª"],["dc.identifier.doi","10.1002/acn3.219"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58419"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/201535/EU//NGIDD"],["dc.relation.euproject","Ngidd"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus-Merzbacher disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Fledrich, R."],["dc.contributor.author","Abdelaal, T."],["dc.contributor.author","Rasch, L."],["dc.contributor.author","Bansal, V."],["dc.contributor.author","Schütza, V."],["dc.contributor.author","Brügger, B."],["dc.contributor.author","Lüchtenborg, C."],["dc.contributor.author","Prukop, T."],["dc.contributor.author","Stenzel, J."],["dc.contributor.author","Rahman, R. U."],["dc.contributor.author","Hermes, D."],["dc.contributor.author","Ewers, D."],["dc.contributor.author","Möbius, W."],["dc.contributor.author","Ruhwedel, T."],["dc.contributor.author","Katona, I."],["dc.contributor.author","Weis, J."],["dc.contributor.author","Klein, D."],["dc.contributor.author","Martini, R."],["dc.contributor.author","Brück, W."],["dc.contributor.author","Müller, W. C."],["dc.contributor.author","Bonn, S."],["dc.contributor.author","Bechmann, I."],["dc.contributor.author","Nave, K. A."],["dc.contributor.author","Stassart, R. M."],["dc.contributor.author","Sereda, M. W."],["dc.date.accessioned","2020-12-10T18:09:47Z"],["dc.date.available","2020-12-10T18:09:47Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41467-018-05420-0"],["dc.identifier.eissn","2041-1723"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15603"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73759"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0209752"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PlOS ONE"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Stenzel, Jan"],["dc.contributor.author","Wernick, Stephanie"],["dc.contributor.author","Kungl, Theresa"],["dc.contributor.author","Mroczek, Magdalena"],["dc.contributor.author","Adam, Julia"],["dc.contributor.author","Ewers, David"],["dc.contributor.author","Nabirotchkin, Serguei"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hajj, Rodolphe"],["dc.contributor.author","Cohen, Daniel"],["dc.contributor.author","Sereda, Michael W."],["dc.date.accessioned","2019-07-09T11:50:18Z"],["dc.date.available","2019-07-09T11:50:18Z"],["dc.date.issued","2019"],["dc.description.abstract","The most common type of Charcot-Marie-Tooth disease is caused by a duplication of PMP22 leading to dysmyelination, axonal loss and progressive muscle weakness (CMT1A). Currently, no approved therapy is available for CMT1A patients. A novel polytherapeutic proof-of-principle approach using PXT3003, a low-dose combination of baclofen, naltrexone and sorbitol, slowed disease progression after long-term dosing in adult Pmp22 transgenic rats, a known animal model of CMT1A. Here, we report an early postnatal, short-term treatment with PXT3003 in CMT1A rats that delays disease onset into adulthood. CMT1A rats were treated from postnatal day 6 to 18 with PXT3003. Behavioural, electrophysiological, histological and molecular analyses were performed until 12 weeks of age. Daily oral treatment for approximately 2 weeks ameliorated motor deficits of CMT1A rats reaching wildtype levels. Histologically, PXT3003 corrected the disturbed axon calibre distribution with a shift towards large motor axons. Despite dramatic clinical amelioration, only distal motor latencies were improved and correlated with phenotype performance. On the molecular level, PXT3003 reduced Pmp22 mRNA overexpression and improved the misbalanced downstream PI3K-AKT / MEK-ERK signalling pathway. The improved differentiation status of Schwann cells may have enabled better long-term axonal support function. We conclude that short-term treatment with PXT3003 during early development may partially prevent the clinical and molecular manifestations of CMT1A. Since PXT3003 has a strong safety profile and is currently undergoing a phase III trial in CMT1A patients, our results suggest that PXT3003 therapy may be a bona fide translatable therapy option for children and young adolescent patients suffering from CMT1A."],["dc.identifier.doi","10.1371/journal.pone.0209752"],["dc.identifier.pmid","30650121"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15906"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59743"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Early short-term PXT3003 combinational therapy delays disease onset in a transgenic rat model of Charcot-Marie-Tooth disease 1A (CMT1A)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1297"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Rafehi, Muhammad"],["dc.contributor.author","Faltraco, Frank"],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Grytzmann, Aileen"],["dc.contributor.author","Berger, Ralf Günter"],["dc.contributor.author","Krings, Ulrich"],["dc.contributor.author","Vormfelde, Stefan Viktor"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Blome, Felix G."],["dc.date.accessioned","2020-10-22T08:52:50Z"],["dc.date.available","2020-10-22T08:52:50Z"],["dc.date.issued","2019"],["dc.description.abstract","Tyramine, formed by the decarboxylation of tyrosine, is a natural constituent of numerous food products. As an indirect sympathomimetic, it can have potentially dangerous hypertensive effects. In vitro data indicated that the pharmacokinetics of tyramine possibly depend on the organic cation transporter OCT1 genotype and on the CYP2D6 genotype. Since tyramine is a prototypic substrate of monoamine oxidase A (MAO-A), genetic polymorphisms in MAO-A may also be relevant. The aims of this study were to identify to what extent the interindividual variation in pharmacokinetics and pharmacodynamics of tyramine is determined by genetic polymorphisms in OCT1, CYP2D6, and MAO-A. Beyond that, we wanted to evaluate tyramine as probe drug for the in vivo activity of MAO-A and OCT1. Therefore, the pharmacokinetics, pharmacodynamics, and pharmacogenetics of tyramine were studied in 88 healthy volunteers after oral administration of a 400 mg dose. We observed a strong interindividual variation in systemic tyramine exposure, with a mean AUC of 3.74 min µg/ml and a high mean CL/F ratio of 107 l/min. On average, as much as 76.8% of the dose was recovered in urine in form of the MAO-catalysed metabolite 4-hydroxyphenylacetic acid (4-HPAA), confirming that oxidative deamination by MAO-A is the quantitatively most relevant metabolic pathway. Systemic exposure of 4-HPAA varied only up to 3-fold, indicating no strong heritable variation in peripheral MAO-A activity. Systolic blood pressure increased by more than 10 mmHg in 71% of the volunteers and correlated strongly with systemic tyramine concentration. In less than 10% of participants, individually variable blood pressure peaks by >40 mmHg above baseline were observed at tyramine concentrations of >60 µg/l. Unexpectedly, the functionally relevant polymorphisms in OCT1 and CYP2D6, including the CYP2D6 poor and ultra-rapid metaboliser genotypes, did not significantly affect tyramine pharmacokinetics or pharmacodynamics. Also, the MOA-A genotypes, which had been associated in several earlier studies with neuropsychiatric phenotypes, had no significant effects on tyramine pharmacokinetics or its metabolism to 4-HPAA. Thus, variation in tyramine pharmacokinetics and pharmacodynamics is not explained by obvious genomic variation, and human tyramine metabolism did not indicate the existence of ultra-low or -high MAO-A activity."],["dc.identifier.doi","10.3389/fphar.2019.01297"],["dc.identifier.pmid","31736764"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16579"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68027"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1663-9812"],["dc.relation.issn","1663-9812"],["dc.relation.orgunit","Institut für Klinische Pharmakologie"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Highly Variable Pharmacokinetics of Tyramine in Humans and Polymorphisms in OCT1, CYP2D6, and MAO-A"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]