@phdthesis{Berg2008,
  author    = {Berg, Daniela},
  title     = {Entwicklung von TRAIL-Fusionsproteinen und ihre Wirkung auf Myelomzellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27430},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {1. Zusammenfassung L{\"o}sliche humane TRAIL-Varianten (hTRAIL), die nur die "TNF homology domain" (THD) beinhalten, binden sowohl den TRAILR1 aus auch den TRAILR2, stimulieren jedoch nur den TRAILR1. Nach sekund{\"a}rem Quervernetzen des Liganden wird dann aber auch der TRAILR2 effektiv aktiviert. Entsprechende murine TRAIL-Varianten (mTRAIL) dagegen zeigen nur eine schwache Rezeptorbindung und sind selbst nach sekund{\"a}rem Quervernetzen nur wenig aktiv. Interessanterweise kann ein Fusionsprotein aus der THD von mTRAIL und der Trimerisierungsdom{\"a}ne von Tenascin-C (TNC), das wie mTRAIL selbst auch als Trimer vorligt, effizient an TRAIL-Rezeptoren binden und nach sekund{\"a}rem Quervernetzen den TRAILR2 gut stimulieren. Weiterhin kann eine mTRAIL-Variante, die neben der THD auch die Stammregion des Molek{\"u}ls enth{\"a}lt, die die THD von der Transmembrandom{\"a}ne trennt, nach sekund{\"a}rem Quervernetzen Apoptose induzieren, jedoch nicht so effektiv wie das TNC-mTRAILFusionsprotein. Die spezifische Bioaktivit{\"a}t der humanen TRAIL-Varianten wird gleichfalls, wenn auch weniger stark, durch Fusion mit der Tenascin-C-Trimerisierungsdom{\"a}ne gesteigert. Die Fixierung des N-Terminus der THD, die hier durch die TNCDom{\"a}ne sonst jedoch durch die Stamm- oder Transmembrandom{\"a}ne gew{\"a}hrleistet wird, k{\"o}nnte demnach f{\"u}r mTRAIL f{\"u}r eine gute Rezeptorbindung und effektive Apoptoseinduktion n{\"o}tig sein. Dies deutet auf eine bisher nicht erkannte Rolle der Stammregion f{\"u}r die Aktivit{\"a}t dieser Liganden hin und bietet die M{\"o}glichkeit, rekombinante l{\"o}sliche Liganden der TNF-Familie mit erh{\"o}hter Aktivit{\"a}t zu generieren. Die TRAIL-induzierte Apoptose kann f{\"u}r die Behandlung von Tumorzellen n{\"u}tzlich sein. Es wurde jedoch k{\"u}rzlich gezeigt, dass TRAIL neben Apoptose auch proinflammatorische, d. h. potentiell tumorf{\"o}rdernde Signalwege, insbesondere in apoptoseresistenten Zellen induzieren kann. Im Folgenden sollte untersucht werden, inwiefern TRAIL solche Signalwege in Myelomzellen stimuliert. Oligomerisiertes TRAIL kann bei allen analysierten Zelllinien Caspasen aktivieren und Apoptose induzieren. Werden die Zelllinien mit dem pan-Caspaseinhibitor ZVAD behandelt, kann die Caspase- Aktivierung bei allen Zellen blockiert werden, die Apoptoseinduktion jedoch nur bei zwei Zelllinien. Im Gegensatz dazu sch{\"u}tzt ZVAD drei andere Myelomzelllinien nur partiell vor der TRAIL-induzierten Apoptose. Dies zeigt, dass TRAIL in Myelomzellen auch caspaseunabh{\"a}ngigen Zelltod induzieren kann. TRAIL induziert in den Myelomzellen auch proinflammatorische Signalwege wie den NF\&\#1082;B-, den JNK-, den p38- und den p42/44-Signalweg. Die Stimulation des JNK- und des p38-Signalwegs erwies sich hierbei in zelltypspezifischer Weise caspaseabh{\"a}ngig, die Aktivierung des NF\&\#1082;B- und p42/44-Signalwegs immer als caspaseunabh{\"a}ngig. Zusammenfassend geht aus diesen Ergebnissen hervor, dass zur Behandlung des multiplen Myeloms, TRAIL in Kombination mit anti-inflammatorisch wirkenden Mitteln eingesetzt werden sollte, insbesondere um m{\"o}gliche proinflammatorische Nebenwirkungen durch TRAIL zu minimieren.},
  subject      = {TRAIL},
  language  = {de}
}
@article{GerlachMaetzlerBroichetal.2012,
  author    = {Gerlach, Manfred and Maetzler, Walter and Broich, Karl and Hampel, Harald and Rems, Lucas and Reum, Torsten and Riederer, Peter and St{\"a}ffler, Albrecht and Streffer, Johannes and Berg, Daniela},
  title     = {Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics},
  series = {Journal of Neural Transmission},
  volume    = {119},
  journal   = {Journal of Neural Transmission},
  number    = {1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125375},
  pages     = {39-52},
  year      = {2012},
  abstract  = {Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.},
  language  = {en}
}
@article{GerlachMaetzlerBroichetal.2011,
  author    = {Gerlach, Manfred and Maetzler, Walter and Broich, Karl and Hampel, Harald and Rems, Lucas and Reum, Torsten and Riederer, Peter and St{\"o}ffler, Albrecht and Streffer, Johannes and Berg, Daniela},
  title     = {Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics},
  series = {Journal of Neural Transmission},
  volume    = {119},
  journal   = {Journal of Neural Transmission},
  number    = {1},
  doi       = {10.1007/s00702-011-0682-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133856},
  pages     = {39-52},
  year      = {2011},
  abstract  = {Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.},
  language  = {en}
}
@article{GschmackMonoranuMaroufetal.2022,
  author    = {Gschmack, Eva and Monoranu, Camelia-Maria and Marouf, Hecham and Meyer, Sarah and Lessel, Lena and Idris, Raja and Berg, Daniela and Maetzler, Walter and Steigerwald, Frank and Volkmann, Jens and Gerlach, Manfred and Riederer, Peter and Koutsilieri, Eleni and Scheller, Carsten},
  title     = {Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson's disease},
  series = {Journal of Neural Transmission},
  volume    = {129},
  journal   = {Journal of Neural Transmission},
  number    = {5-6},
  doi       = {10.1007/s00702-022-02495-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325161},
  pages     = {545-555},
  year      = {2022},
  abstract  = {Idiopathic Parkinson's disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus-subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood-brain barrier.},
  language  = {en}
}
@article{MuellerGirardHopfneretal.2016,
  author    = {M{\"u}ller, Stefanie H. and Girard, Simon L. and Hopfner, Franziska and Merner, Nancy D. and Bourassa, Cynthia V. and Lorenz, Delia and Clark, Lorraine N. and Tittmann, Lukas and Soto-Ortolaza, Alexandra I. and Klebe, Stephan and Hallett, Mark and Schneider, Susanne A. and Hodgkinson, Colin A. and Lieb, Wolfgang and Wszolek, Zbigniew K. and Pendziwiat, Manuela and Lorenzo-Betancor, Oswaldo and Poewe, Werner and Ortega-Cubero, Sara and Seppi, Klaus and Rajput, Alex and Hussl, Anna and Rajput, Ali H. and Berg, Daniela and Dion, Patrick A. and Wurster, Isabel and Shulman, Joshua M. and Srulijes, Karin and Haubenberger, Dietrich and Pastor, Pau and Vilari{\~n}o-G{\"u}ell, Carles and Postuma, Ronald B. and Bernard, Genevi{\`e}ve and Ladwig, Karl-Heinz and Dupr{\´e}, Nicolas and Jankovic, Joseph and Strauch, Konstantin and Panisset, Michel and Winkelmann, Juliane and Testa, Claudia M. and Reischl, Eva and Zeuner, Kirsten E. and Ross, Owen A. and Arzberger, Thomas and Chouinard, Sylvain and Deuschl, G{\"u}nther and Louis, Elan D. and Kuhlenb{\"a}umer, Gregor and Rouleau, Guy A.},
  title     = {Genome-wide association study in essential tremor identifies three new loci},
  series = {Brain},
  volume    = {139},
  journal   = {Brain},
  doi       = {10.1093/brain/aww242},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186541},
  pages     = {3163-3169},
  year      = {2016},
  abstract  = {We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.},
  language  = {en}
}