Reinert, Marie-Christine

[["dc.bibliographiccitation.artnumber","64"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Catarino, Claudia B."],["dc.contributor.author","Klopstock, Thomas"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Schittkowski, Michael Peter"],["dc.contributor.author","Wilichowski, Ekkehard"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.issued","2021"],["dc.date.updated","2022-07-29T12:17:42Z"],["dc.description.abstract","Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV. Results We describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control. Conclusions Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Orphanet Journal of Rare Diseases. 2021 Feb 04;16(1):64"],["dc.identifier.doi","10.1186/s13023-021-01690-y"],["dc.identifier.pmid","33541401"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82509"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/219"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.eissn","1750-1172"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Sulthiame"],["dc.subject","Carbonic anhydrase inhibitor"],["dc.subject","Adverse effects"],["dc.subject","Leber hereditary optic neuropathy"],["dc.subject","LHON"],["dc.subject","Oxygen consumption rate"],["dc.title","Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e980"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Schulz, R."],["dc.contributor.author","Streller, F."],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Reinert, M. C."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Marchenko, N. D."],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:46:24Z"],["dc.date.available","2018-11-07T09:46:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Overexpression of the human epidermal growth factor receptor-2 (HER2) in breast cancer strongly correlates with aggressive tumors and poor prognosis. Recently, a positive correlation between HER2 and MIF (macrophage migration inhibitory factor, a tumor-promoting protein and heat-shock protein 90 (HSP90) client) protein levels was shown in cancer cells. However, the underlying mechanistic link remained unknown. Here we show that overexpressed HER2 constitutively activates heat-shock factor 1 (HSF1), the master transcriptional regulator of the inducible proteotoxic stress response of heat-shock chaperones, including HSP90, and a crucial factor in initiation and maintenance of the malignant state. Inhibiting HER2 pharmacologically by Lapatinib (a dual HER2/epidermal growth factor receptor inhibitor) or CP724.714 (a specific HER2 inhibitor), or by knockdown via siRNA leads to inhibition of phosphoactivated Ser326 HSF1, and subsequently blocks the activity of the HSP90 chaperone machinery in HER2-overexpressing breast cancer lines. Consequently, HSP90 clients, including MIF, AKT, mutant p53 and HSF1 itself, become destabilized, which in turn inhibits tumor proliferation. Mechanistically, HER2 signals via the phosphoinositide-3kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) axis to induce activated pSer326 HSF1. Heat-shock stress experiments confirm this functional link between HER2 and HSF1, as HER2 (and PI3K) inhibition attenuate the HSF1-mediated heat-shock response. Importantly, we confirmed this axis in vivo. In the mouse model of HER2-driven breast cancer, ErbB2 inhibition by Lapatinib strongly suppresses tumor progression, and this is associated with inactivation of the HSF1 pathway. Moreover, ErbB2-overexpressing cancer cells derived from a primary mouse ErbB2 tumor also show HSF1 inactivation and HSP90 client destabilization in response to ErbB2 inhibition. Furthermore, in HER2-positive human breast cancers HER2 levels strongly correlate with pSer326 HSF1 activity. Our results show for the first time that HER2/ErbB2 overexpression controls HSF1 activity, with subsequent stabilization of numerous tumor-promoting HSP90 clients such as MIF, AKT and HSF1 itself, thereby causing a robust promotion in tumor growth in HER2-positive breast cancer."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1038/cddis.2013.508"],["dc.identifier.isi","000332222700004"],["dc.identifier.pmid","24384723"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9556"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34861"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer"],["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.firstpage","e749"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neurology - Neuroimmunology Neuroinflammation"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Benkert, Pascal"],["dc.contributor.author","Wuerfel, Jens"],["dc.contributor.author","Michalak, Zuzanna"],["dc.contributor.author","Ruberte, Esther"],["dc.contributor.author","Barro, Christian"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Stark, Wiebke"],["dc.contributor.author","Kropshofer, Harald"],["dc.contributor.author","Tomic, Davorka"],["dc.contributor.author","Leppert, David"],["dc.contributor.author","Kuhle, Jens"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-04-14T08:25:14Z"],["dc.date.available","2021-04-14T08:25:14Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1212/NXI.0000000000000749"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17477"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81564"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2332-7812"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","34"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Lagumersindez-Denis, Nielsen"],["dc.contributor.author","Wrzos, Claudia"],["dc.contributor.author","Mack, Matthias"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Hollasch, Heiko"],["dc.contributor.author","Flach, Anne"],["dc.contributor.author","Bruehl, Hilke"],["dc.contributor.author","Cullen, Eilish"],["dc.contributor.author","Schlumbohm, Christina"],["dc.contributor.author","Fuchs, Eberhard"],["dc.contributor.author","Linington, Christopher"],["dc.contributor.author","Barrantes-Freer, Alonso"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Wegner, Christiane"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Nessler, Stefan"],["dc.date.accessioned","2018-11-07T10:22:07Z"],["dc.date.available","2018-11-07T10:22:07Z"],["dc.date.issued","2017"],["dc.description.abstract","Cortical demyelination is a widely recognized hallmark of multiple sclerosis (MS) and correlate of disease progression and cognitive decline. The pathomechanisms initiating and driving gray matter damage are only incompletely understood. Here, we determined the infiltrating leukocyte subpopulations in 26 cortical demyelinated lesions of biopsied MS patients and assessed their contribution to cortical lesion formation in a newly developed mouse model. We find that conformation-specific anti-myelin antibodies contribute to cortical demyelination even in the absence of the classical complement pathway. T cells and natural killer cells are relevant for intracortical type 2 but dispensable for subpial type 3 lesions, whereas CCR2(+) monocytes are required for both. Depleting CCR2(+) monocytes in marmoset monkeys with experimental autoimmune encephalomyelitis using a novel humanized CCR2 targeting antibody translates into significantly less cortical demyelination and disease severity. We conclude that biologics depleting CCR2(+) monocytes might be attractive candidates for preventing cortical lesion formation and ameliorating disease progression in MS."],["dc.identifier.doi","10.1007/s00401-017-1706-x"],["dc.identifier.isi","000403235900002"],["dc.identifier.pmid","28386765"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14713"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42218"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Differential contribution of immune effector mechanisms to cortical demyelination in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]