Eichele, Gregor

[["dc.bibliographiccitation.firstpage","560a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dervisoglu, Riza"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Wegstroth, Melanie"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Lee, Joon"],["dc.contributor.author","Lal, Ratneshwar"],["dc.contributor.author","Eichele, Gregor"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2022-03-01T11:44:59Z"],["dc.date.available","2022-03-01T11:44:59Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.bpj.2017.11.3064"],["dc.identifier.pii","S0006349517342960"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103181"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","The Small Molecule anle138b Shows Interaction with α-Synuclein Oligomers in Phospholipid Membranes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","32"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","EMBO molecular medicine"],["dc.bibliographiccitation.lastpage","47"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Martinez-Hernandez, Ana"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Gillman, Alan L."],["dc.contributor.author","Lee, Joon"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Agbemenyah, Hope Y."],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Kaurani, Lalit"],["dc.contributor.author","Grigorian, Gayane"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Wilken, Petra"],["dc.contributor.author","Teran Arce, Fernando"],["dc.contributor.author","Wagner, Jens"],["dc.contributor.author","Fuhrman, Martin"],["dc.contributor.author","Caruana, Mario"],["dc.contributor.author","Camilleri, Angelique"],["dc.contributor.author","Vassallo, Neville"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Benz, Roland"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Korte, Martin"],["dc.contributor.author","Lal, Ratnesh"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Eichele, Gregor"],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2018-01-09T14:58:18Z"],["dc.date.available","2018-01-09T14:58:18Z"],["dc.date.issued","2017-12-05"],["dc.description.abstract","Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level, we provide evidence that anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further."],["dc.identifier.doi","10.15252/emmm.201707825"],["dc.identifier.pmid","29208638"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11613"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1757-4684"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Martinez Hernandez, Ana"],["dc.contributor.author","Silbern, Ivan"],["dc.contributor.author","Geffers, Insa"],["dc.contributor.author","Tatenhorst, Lars"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Eichele, Gregor"],["dc.date.accessioned","2021-08-12T07:45:45Z"],["dc.date.available","2021-08-12T07:45:45Z"],["dc.date.issued","2021"],["dc.description.abstract","α-synuclein (αSyn) is the main protein component of Lewy bodies, intracellular inclusions found in the brain of Parkinson’s disease (PD) patients. Neurotoxic αSyn species are broadly modified post-translationally and, in patients with genetic forms of PD, carry genetically encoded amino acid substitutions. Mutations and C-terminal truncation can increase αSyn oligomerization and fibrillization. Although several genetic mouse models based on αSyn mutations and/or truncations exist, there is still a lack of mouse models for synucleinopathies not relying on overexpression. We report here two synucleinopathy mouse models, which are based on a triple alanine to proline mutation and a C-terminal truncation of αSyn, but do not overexpress the mutant protein when compared to the endogenous mouse protein. We knocked h αSyn TP or h αSyn Δ119 (h stands for “human”) into the murine αSyn locus. hαSyn TP is a structure-based mutant with t riple alanine to p roline substitutions that favors oligomers, is neurotoxic and evokes PD-like symptoms in Drosophila melanogaster . hαSyn Δ119 lacks 21 amino acids at the C-terminus, favors fibrillary aggregates and occurs in PD. Knocking-in of h αSyn TP or h αSyn Δ119 into the murine αSyn locus places the mutant protein under the control of the endogenous regulatory elements while simultaneously disrupting the mαSyn gene. Mass spectrometry revealed that h αSyn TP and h αSyn Δ119 mice produced 12 and 10 times less mutant protein, compared to mαSyn in wild type mice. We show phenotypes in 1 and 1.5 years old hαSyn TP and hαSyn Δ119 mice, despite the lower levels of hαSyn TP and hαSyn Δ119 expression. Direct comparison of the two mouse models revealed many commonalities but also aspects unique to each model. Commonalities included strong immunoactive state, impaired olfaction and motor coordination deficits. Neither model showed DAergic neuronal loss. Impaired climbing abilities at 1 year of age and a deviant gait pattern at 1.5 years old were specific for hαSyn Δ119 mice, while a compulsive behavior was exclusively detected in hαSyn TP mice starting at 1 year of age. We conclude that even at very moderate levels of expression the two αSyn variants evoke measurable and progressive deficiencies in mutant mice. The two transgenic mouse models can thus be suitable to study αSyn-variant-based pathology in vivo and test new therapeutic approaches."],["dc.description.abstract","α-synuclein (αSyn) is the main protein component of Lewy bodies, intracellular inclusions found in the brain of Parkinson’s disease (PD) patients. Neurotoxic αSyn species are broadly modified post-translationally and, in patients with genetic forms of PD, carry genetically encoded amino acid substitutions. Mutations and C-terminal truncation can increase αSyn oligomerization and fibrillization. Although several genetic mouse models based on αSyn mutations and/or truncations exist, there is still a lack of mouse models for synucleinopathies not relying on overexpression. We report here two synucleinopathy mouse models, which are based on a triple alanine to proline mutation and a C-terminal truncation of αSyn, but do not overexpress the mutant protein when compared to the endogenous mouse protein. We knocked h αSyn TP or h αSyn Δ119 (h stands for “human”) into the murine αSyn locus. hαSyn TP is a structure-based mutant with t riple alanine to p roline substitutions that favors oligomers, is neurotoxic and evokes PD-like symptoms in Drosophila melanogaster . hαSyn Δ119 lacks 21 amino acids at the C-terminus, favors fibrillary aggregates and occurs in PD. Knocking-in of h αSyn TP or h αSyn Δ119 into the murine αSyn locus places the mutant protein under the control of the endogenous regulatory elements while simultaneously disrupting the mαSyn gene. Mass spectrometry revealed that h αSyn TP and h αSyn Δ119 mice produced 12 and 10 times less mutant protein, compared to mαSyn in wild type mice. We show phenotypes in 1 and 1.5 years old hαSyn TP and hαSyn Δ119 mice, despite the lower levels of hαSyn TP and hαSyn Δ119 expression. Direct comparison of the two mouse models revealed many commonalities but also aspects unique to each model. Commonalities included strong immunoactive state, impaired olfaction and motor coordination deficits. Neither model showed DAergic neuronal loss. Impaired climbing abilities at 1 year of age and a deviant gait pattern at 1.5 years old were specific for hαSyn Δ119 mice, while a compulsive behavior was exclusively detected in hαSyn TP mice starting at 1 year of age. We conclude that even at very moderate levels of expression the two αSyn variants evoke measurable and progressive deficiencies in mutant mice. The two transgenic mouse models can thus be suitable to study αSyn-variant-based pathology in vivo and test new therapeutic approaches."],["dc.identifier.doi","10.3389/fnins.2021.643391"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88545"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/313"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/126"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["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","1662-453X"],["dc.relation.workinggroup","RG Griesinger"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Low-Expressing Synucleinopathy Mouse Models Based on Oligomer-Forming Mutations and C-Terminal Truncation of α-Synuclein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","352a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dervisoglu, Riza"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Wegstroth, Melanie"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Benz, Roland"],["dc.contributor.author","Eichele, Gregor"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2022-03-01T11:45:00Z"],["dc.date.available","2022-03-01T11:45:00Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.bpj.2018.11.1913"],["dc.identifier.pii","S0006349518331783"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103185"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Protein-Drug Interactions in the Membrane: The Small Molecule Anle138b and its Binding to α-Synuclein Oligomers"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]