Voigt, Aaron

[["dc.bibliographiccitation.artnumber","e12247"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PloS one"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Herholz, David"],["dc.contributor.author","Fiesel, Fabienne C."],["dc.contributor.author","Kaur, Kavita"],["dc.contributor.author","Müller, Daniel"],["dc.contributor.author","Karsten, Peter"],["dc.contributor.author","Weber, Stephanie S."],["dc.contributor.author","Kahle, Philipp J."],["dc.contributor.author","Marquardt, Till"],["dc.contributor.author","Schulz, Jörg"],["dc.date.accessioned","2019-07-09T11:53:07Z"],["dc.date.available","2019-07-09T11:53:07Z"],["dc.date.issued","2010"],["dc.description.abstract","Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear--a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated neurotoxicity in vivo."],["dc.identifier.doi","10.1371/journal.pone.0012247"],["dc.identifier.fs","573853"],["dc.identifier.pmid","20806063"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6913"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60347"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.subject.ddc","610"],["dc.subject.mesh","Amyotrophic Lateral Sclerosis"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Cell Line"],["dc.subject.mesh","Chickens"],["dc.subject.mesh","DNA-Binding Proteins"],["dc.subject.mesh","Drosophila melanogaster"],["dc.subject.mesh","Frontotemporal Lobar Degeneration"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Intracellular Space"],["dc.subject.mesh","Locomotion"],["dc.subject.mesh","Longevity"],["dc.subject.mesh","Male"],["dc.subject.mesh","Motor Neurons"],["dc.subject.mesh","Mutation"],["dc.subject.mesh","Neurons"],["dc.subject.mesh","Organ Specificity"],["dc.subject.mesh","Protein Binding"],["dc.subject.mesh","Protein Transport"],["dc.subject.mesh","RNA"],["dc.title","TDP-43-mediated neuron loss in vivo requires RNA-binding activity."],["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","e1002488"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Butler, Erin K."],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Lutz, A. Kathrin"],["dc.contributor.author","Toegel, Jane Patricia"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Karsten, Peter"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Reinartz, Andrea"],["dc.contributor.author","Winklhofer, Konstanze F."],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T09:13:43Z"],["dc.date.available","2018-11-07T09:13:43Z"],["dc.date.issued","2012"],["dc.description.abstract","Overexpression or mutation of alpha-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T] alpha-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T] alpha-Synuclein expression. In addition, decreased TRAP1 expression in [A53T] alpha-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T] alpha-Synuclein-induced sensitivity to rotenone treatment. In human (non) neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T] alpha-Synuclein-induced sensitivity to oxidative stress treatment. [A53T] alpha-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T] alpha-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T] alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to alpha-Synuclein."],["dc.identifier.doi","10.1371/journal.pgen.1002488"],["dc.identifier.isi","000300725500013"],["dc.identifier.pmid","22319455"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7775"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27236"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7390"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Mitochondrial Chaperone Protein TRAP1 Mitigates alpha-Synuclein Toxicity"],["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","e47452"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Vossfeldt, Hannes"],["dc.contributor.author","Butzlaff, Malte"],["dc.contributor.author","Pruessing, Katja"],["dc.contributor.author","Charthaigh, Roisin-Ana Ni"],["dc.contributor.author","Karsten, Peter"],["dc.contributor.author","Lankes, Anne"],["dc.contributor.author","Hamm, Sabine"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Adryan, Boris"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Voigt, Aaron"],["dc.date.accessioned","2018-11-07T09:03:34Z"],["dc.date.available","2018-11-07T09:03:34Z"],["dc.date.issued","2012"],["dc.description.abstract","Polyglutamine (polyQ) diseases represent a neuropathologically heterogeneous group of disorders. The common theme of these disorders is an elongated polyQ tract in otherwise unrelated proteins. So far, only symptomatic treatment can be applied to patients suffering from polyQ diseases. Despite extensive research, the molecular mechanisms underlying polyQ-induced toxicity are largely unknown. To gain insight into polyQ pathology, we performed a large-scale RNAi screen in Drosophila to identify modifiers of toxicity induced by expression of truncated Ataxin-3 containing a disease-causing polyQ expansion. We identified various unknown modifiers of polyQ toxicity. Large-scale analysis indicated a dissociation of polyQ aggregation and toxicity."],["dc.identifier.doi","10.1371/journal.pone.0047452"],["dc.identifier.isi","000310741400022"],["dc.identifier.pmid","23139745"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8321"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24922"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Large-Scale Screen for Modifiers of Ataxin-3-Derived Polyglutamine-Induced Toxicity in Drosophila"],["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"]]