Martinez-Hernandez, Ana

[["dc.bibliographiccitation.firstpage","232"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Genomics"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Cankaya, Murat"],["dc.contributor.author","Hernandez, Ana"],["dc.contributor.author","Ciftci, Mehmet"],["dc.contributor.author","Beydemir, Sukru"],["dc.contributor.author","Ozdemir, Hasan"],["dc.contributor.author","Budak, Harun"],["dc.contributor.author","Gulcin, Ilhami"],["dc.contributor.author","Comakli, Veysel"],["dc.contributor.author","Emircupani, Tufan"],["dc.contributor.author","Kufrevioglu, Omer"],["dc.date.accessioned","2021-06-01T10:47:59Z"],["dc.date.available","2021-06-01T10:47:59Z"],["dc.date.issued","2007"],["dc.identifier.doi","10.1186/1471-2164-8-232"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85786"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","1471-2164"],["dc.title","An analysis of expression patterns of genes encoding proteins with catalytic activities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","1912"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","1927"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Stilling, Roman Manuel"],["dc.contributor.author","Roenicke, Raik"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Bahari-Javan, Sanaz"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Sananbenesi, Farahnaz"],["dc.contributor.author","Schuetz, Anna L."],["dc.contributor.author","Dyczkowski, Jerzy"],["dc.contributor.author","Martinez-Hernandez, Ana"],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Dent, Sharon Y. R."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Reymann, Klaus G."],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2017-09-07T11:45:35Z"],["dc.date.available","2017-09-07T11:45:35Z"],["dc.date.issued","2014"],["dc.description.abstract","Neuronal histone acetylation has been linked to memory consolidation, and targeting histone acetylation has emerged as a promising therapeutic strategy for neuropsychiatric diseases. However, the role of histone-modifying enzymes in the adult brain is still far from being understood. Here we use RNA sequencing to screen the levels of all known histone acetyltransferases (HATs) in the hippocampal CA1 region and find that K-acetyltransferase 2a (Kat2a)-a HAT that has not been studied for its role in memory function so far-shows highest expression. Mice that lack Kat2a show impaired hippocampal synaptic plasticity and long-term memory consolidation. We furthermore show that Kat2a regulates a highly interconnected hippocampal gene expression network linked to neuroactive receptor signaling via a mechanism that involves nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B). In conclusion, our data establish Kat2a as a novel and essential regulator of hippocampal memory consolidation."],["dc.identifier.doi","10.15252/embj.201487870"],["dc.identifier.gro","3142062"],["dc.identifier.isi","000341839500009"],["dc.identifier.pmid","25024434"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4123"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6058"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","6063"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Heneka, Michael T."],["dc.contributor.author","Nadrigny, Fabian"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Martinez-Hernandez, Ana"],["dc.contributor.author","Dumitrescu-Ozimek, Lucia"],["dc.contributor.author","Terwel, Dick"],["dc.contributor.author","Jardanhazi-Kurutz, Daniel"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Kummer, Markus P."],["dc.date.accessioned","2018-11-07T08:44:59Z"],["dc.date.available","2018-11-07T08:44:59Z"],["dc.date.issued","2010"],["dc.description.abstract","Locus ceruleus (LC)-supplied norepinephrine (NE) suppresses neuroinflammation in the brain. To elucidate the effect of LC degeneration and subsequent NE deficiency on Alzheimer's disease pathology, we evaluated NE effects on microglial key functions. NE stimulation of mouse microglia suppressed A beta-induced cytokine and chemokine production and increased microglial migration and phagocytosis of A beta. Induced degeneration of the locus ceruleus increased expression of inflammatory mediators in APP-transgenic mice and resulted in elevated A beta deposition. In vivo laser microscopy confirmed a reduced recruitment of microglia to A beta plaque sites and impaired microglial A beta phagocytosis in NE-depleted APP-transgenic mice. Supplying the mice the norepinephrine precursor L-threo-DOPS restored microglial functions in NE-depleted mice. This indicates that decrease of NE in locus ceruleus projection areas facilitates the inflammatory reaction of microglial cells in AD and impairs microglial migration and phagocytosis, thereby contributing to reduced A beta clearance. Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion."],["dc.identifier.doi","10.1073/pnas.0909586107"],["dc.identifier.isi","000276159500066"],["dc.identifier.pmid","20231476"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20326"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]