Sereda, Michael Werner

[["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.artnumber","201"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Orphanet journal of rare diseases"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Chumakov, Ilya"],["dc.contributor.author","Milet, Aude"],["dc.contributor.author","Cholet, Nathalie"],["dc.contributor.author","Primas, Gwenaël"],["dc.contributor.author","Boucard, Aurélie"],["dc.contributor.author","Pereira, Yannick"],["dc.contributor.author","Graudens, Esther"],["dc.contributor.author","Mandel, Jonas"],["dc.contributor.author","Laffaire, Julien"],["dc.contributor.author","Foucquier, Julie"],["dc.contributor.author","Glibert, Fabrice"],["dc.contributor.author","Bertrand, Viviane"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Vial, Emmanuel"],["dc.contributor.author","Guedj, Mickaël"],["dc.contributor.author","Hajj, Rodolphe"],["dc.contributor.author","Nabirotchkin, Serguei"],["dc.contributor.author","Cohen, Daniel"],["dc.date.accessioned","2019-07-09T11:41:08Z"],["dc.date.available","2019-07-09T11:41:08Z"],["dc.date.issued","2014"],["dc.description.abstract","Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited sensory and motor peripheral neuropathy. It is caused by PMP22 overexpression which leads to defects of peripheral myelination, loss of long axons, and progressive impairment then disability. There is no treatment available despite observations that monotherapeutic interventions slow progression in rodent models. We thus hypothesized that a polytherapeutic approach using several drugs, previously approved for other diseases, could be beneficial by simultaneously targeting PMP22 and pathways important for myelination and axonal integrity. A combination of drugs for CMT1A polytherapy was chosen from a group of authorised drugs for unrelated diseases using a systems biology approach, followed by pharmacological safety considerations. Testing and proof of synergism of these drugs were performed in a co-culture model of DRG neurons and Schwann cells derived from a Pmp22 transgenic rat model of CMT1A. Their ability to lower Pmp22 mRNA in Schwann cells relative to house-keeping genes or to a second myelin transcript (Mpz) was assessed in a clonal cell line expressing these genes. Finally in vivo efficacy of the combination was tested in two models: CMT1A transgenic rats, and mice that recover from a nerve crush injury, a model to assess neuroprotection and regeneration. Combination of (RS)-baclofen, naltrexone hydrochloride and D-sorbitol, termed PXT3003, improved myelination in the Pmp22 transgenic co-culture cellular model, and moderately down-regulated Pmp22 mRNA expression in Schwannoma cells. In both in vitro systems, the combination of drugs was revealed to possess synergistic effects, which provided the rationale for in vivo clinical testing of rodent models. In Pmp22 transgenic CMT1A rats, PXT3003 down-regulated the Pmp22 to Mpz mRNA ratio, improved myelination of small fibres, increased nerve conduction and ameliorated the clinical phenotype. PXT3003 also improved axonal regeneration and remyelination in the murine nerve crush model. Based on these observations in preclinical models, a clinical trial of PTX3003 in CMT1A, a neglected orphan disease, is warranted. If the efficacy of PTX3003 is confirmed, rational polytherapy based on novel combinations of existing non-toxic drugs with pleiotropic effects may represent a promising approach for rapid drug development."],["dc.identifier.doi","10.1186/s13023-014-0201-x"],["dc.identifier.fs","606978"],["dc.identifier.pmid","25491744"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11689"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58355"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1750-1172"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","87"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Schlotter-Weigel, Beate"],["dc.contributor.author","Schnizer, Tuuli J."],["dc.contributor.author","Wichert, Sven P."],["dc.contributor.author","Stassart, Ruth Martha"],["dc.contributor.author","Hoerste, Gerd Meyer Zu"],["dc.contributor.author","Klink, Axel"],["dc.contributor.author","Weiss, Bernhard G."],["dc.contributor.author","Haag, Uwe"],["dc.contributor.author","Walter, Maggie C."],["dc.contributor.author","Rautenstrauss, Bernd"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Rossner, Moritz J."],["dc.contributor.author","Sereda, Michael W."],["dc.date.accessioned","2018-11-07T09:15:45Z"],["dc.date.available","2018-11-07T09:15:45Z"],["dc.date.issued","2012"],["dc.description.abstract","Charcot-Marie-Tooth disease is the most common inherited neuropathy and a duplication of the peripheral myelin protein 22 gene causes the most frequent subform Charcot-Marie-Tooth 1A. Patients develop a slowly progressive dysmyelinating and demyelinating peripheral neuropathy and distally pronounced muscle atrophy. The amount of axonal loss determines disease severity. Although patients share an identical monogenetic defect, the disease progression is strikingly variable and the impending disease course can not be predicted in individual patients. Despite promising experimental data, recent therapy trials have failed. Established clinical outcome measures are thought to be too insensitive to detect amelioration within trials. Surrogate biomarkers of disease severity in Charcot-Marie-Tooth 1A are thus urgently needed. Peripheral myelin protein 22 transgenic rats harbouring additional copies of the peripheral myelin protein 22 gene ('Charcot-Marie-Tooth rats'), which were kept on an outbred background mimic disease hallmarks and phenocopy the variable disease severity of patients with Charcot-Marie-Tooth 1A. Hence, we used the Charcot-Marie-Tooth rat to dissect prospective and surrogate markers of disease severity derived from sciatic nerve and skin tissue messenger RNA extracts. Gene set enrichment analysis of sciatic nerve transcriptomes revealed that dysregulation of lipid metabolism associated genes such as peroxisome proliferator-activated receptor gamma constitutes a modifier of present and future disease severity. Importantly, we directly validated disease severity markers from the Charcot-Marie-Tooth rats in 46 patients with Charcot-Marie-Tooth 1A. Our data suggest that the combination of age and cutaneous messenger RNA levels of glutathione S-transferase theta 2 and cathepsin A composes a strong indicator of disease severity in patients with Charcot-Marie-Tooth 1A, as quantified by the Charcot-Marie-Tooth Neuropathy Score. This translational approach, utilizing a transgenic animal model, demonstrates that transcriptional analysis of skin biopsy is suitable to identify biomarkers of Charcot-Marie-Tooth 1A."],["dc.identifier.doi","10.1093/brain/awr322"],["dc.identifier.isi","000300044400016"],["dc.identifier.pmid","22189569"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27771"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1840"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Akkermann, Dagmar"],["dc.contributor.author","Schütza, Vlad"],["dc.contributor.author","Abdelaal, Tamer A."],["dc.contributor.author","Hermes, Doris"],["dc.contributor.author","Schäffner, Erik"],["dc.contributor.author","Soto-Bernardini, M. Clara"],["dc.contributor.author","Götze, Tilmann"],["dc.contributor.author","Klink, Axel"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Krueger, Martin"],["dc.contributor.author","Kungl, Theresa"],["dc.contributor.author","Frydrychowicz, Clara"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Mueller, Wolf C."],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Schwab, Markus H."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Stassart, Ruth M."],["dc.date.accessioned","2019-07-09T11:51:38Z"],["dc.date.available","2019-07-09T11:51:38Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41467-019-09886-4"],["dc.identifier.pmid","30992451"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59979"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Publisher Correction: NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1467"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Akkermann, Dagmar"],["dc.contributor.author","Schütza, Vlad"],["dc.contributor.author","Abdelaal, Tamer A."],["dc.contributor.author","Hermes, Doris"],["dc.contributor.author","Schäffner, Erik"],["dc.contributor.author","Soto-Bernardini, M. Clara"],["dc.contributor.author","Götze, Tilmann"],["dc.contributor.author","Klink, Axel"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Krueger, Martin"],["dc.contributor.author","Kungl, Theresa"],["dc.contributor.author","Frydrychowicz, Clara"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Mueller, Wolf C."],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Schwab, Markus H."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Stassart, Ruth M."],["dc.date.accessioned","2019-07-09T11:50:53Z"],["dc.date.available","2019-07-09T11:50:53Z"],["dc.date.issued","2019"],["dc.description.abstract","In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental."],["dc.identifier.doi","10.1038/s41467-019-09385-6"],["dc.identifier.pmid","30931926"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59847"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","486"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","499"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Oltrogge, Jan H."],["dc.contributor.author","Wolfer, Susanne"],["dc.contributor.author","Wieser, Georg L."],["dc.contributor.author","Nientiedt, Tobias"],["dc.contributor.author","Pieper, Alexander"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Groszer, Matthias"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2018-11-07T09:09:46Z"],["dc.date.available","2018-11-07T09:09:46Z"],["dc.date.issued","2012"],["dc.description.abstract","Tomacula and myelin outfoldings are striking neuropathological features of a diverse group of inherited demyelinating neuropathies. Whereas the underlying genetic defects are well known, the molecular mechanisms of tomacula formation have remained obscure. We hypothesized that they are caused by uncontrolled, excessive myelin membrane growth, a process, which is regulated in normal development by neuregulin-1/ErbB2, PI3 Kinase signalling and ERK/MAPK signalling. Here, we demonstrate by targeted disruption of Pten in Schwann cells that hyperactivation of the endogenous PI3 Kinase pathway causes focal hypermyelination, myelin outfoldings and tomacula, even when induced in adult animals by tamoxifen, and is associated with progressive peripheral neuropathy. Activated AKT kinase is associated with PtdIns(3,4,5)P3 at paranodal loops and SchmidtLanterman incisures. This striking myelin pathology, with features of human CMT type 4B1 and HNPP, is dependent on AKT/mTOR signalling, as evidenced by a significant amelioration of the pathology in mice treated with rapamycin. We suggest that regions of non-compact myelin are under lifelong protection by PTEN against abnormal membrane outgrowth, and that dysregulated phosphoinositide levels play a critical role in the pathology of tomaculous neuropathies."],["dc.identifier.doi","10.1002/emmm.201200227"],["dc.identifier.isi","000304767900007"],["dc.identifier.pmid","22488882"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7777"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26338"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1757-4676"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Genetic disruption of Pten in a novel mouse model of tomaculous neuropathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.firstpage","355"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","365"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Klinker, Florian"],["dc.contributor.author","Juergens, Tanja"],["dc.contributor.author","Glaser, Raoul"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Brinkmann, Bastian G."],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Guedes, Rubem C. A."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Liebetanz, David"],["dc.date.accessioned","2018-11-07T11:24:30Z"],["dc.date.available","2018-11-07T11:24:30Z"],["dc.date.issued","2009"],["dc.description.abstract","Objective: Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD). Methods: CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type 1 transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein-transgenic mice exhibiting pronounced astrogliosis. Results: Cortical demyelination, but not astrogliosis or inflamation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type 1 transgenic mice displayed a decelerated CSD propagation. Interpretation: Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function."],["dc.identifier.doi","10.1002/ana.21746"],["dc.identifier.isi","000270573700017"],["dc.identifier.pmid","19798729"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56422"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0364-5134"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Propagation of Spreading Depression Inversely Correlates with Cortical Myelin Content"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","53"],["dc.bibliographiccitation.journal","F1000Research"],["dc.bibliographiccitation.lastpage","53"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Ekins, Sean"],["dc.contributor.author","Litterman, Nadia K."],["dc.contributor.author","Arnold, Renée J. G."],["dc.contributor.author","Burgess, Robert W."],["dc.contributor.author","Freundlich, Joel S."],["dc.contributor.author","Gray, Steven J."],["dc.contributor.author","Higgins, Joseph J."],["dc.contributor.author","Langley, Brett"],["dc.contributor.author","Willis, Dianna E."],["dc.contributor.author","Notterpek, Lucia"],["dc.contributor.author","Pleasure, David"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Moore, Allison"],["dc.date.accessioned","2019-07-09T11:42:28Z"],["dc.date.available","2019-07-09T11:42:28Z"],["dc.date.issued","2015"],["dc.description.abstract","This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases."],["dc.identifier.doi","10.12688/f1000research.6160.1"],["dc.identifier.pmid","25901280"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13519"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58677"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2046-1402"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A brief review of recent Charcot-Marie-Tooth research and priorities."],["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"]]