Griesinger, Christian

[["dc.bibliographiccitation.firstpage","12404"],["dc.bibliographiccitation.issue","82"],["dc.bibliographiccitation.journal","Chemical Communications"],["dc.bibliographiccitation.lastpage","12407"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Assfalg, Michael"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2020-12-10T18:11:26Z"],["dc.date.available","2020-12-10T18:11:26Z"],["dc.date.issued","2019"],["dc.description.abstract","This NMR probe of water dynamics enables viscosity determination in concentrated and crowded solutions and allows quantifying internal fluidity within biological condensates."],["dc.description.abstract","We present an NMR method based on natural abundance 17 O relaxation of water to determine effective viscosity in biological aqueous samples. The method accurately captures viscosity of dilute and crowded protein solutions and offers a fairly simple way to quantify the internal fluidity of biological condensates formed through phase separation."],["dc.description.abstract","This NMR probe of water dynamics enables viscosity determination in concentrated and crowded solutions and allows quantifying internal fluidity within biological condensates."],["dc.description.abstract","We present an NMR method based on natural abundance 17 O relaxation of water to determine effective viscosity in biological aqueous samples. The method accurately captures viscosity of dilute and crowded protein solutions and offers a fairly simple way to quantify the internal fluidity of biological condensates formed through phase separation."],["dc.identifier.doi","10.1039/C9CC06124J"],["dc.identifier.eissn","1364-548X"],["dc.identifier.issn","1359-7345"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16666"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74010"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1364-548X"],["dc.relation.issn","1359-7345"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A facile oxygen-17 NMR method to determine effective viscosity in dilute, molecularly crowded and confined aqueous media"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eabg2174"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Science Advances"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dervişoğlu, Rıza"],["dc.contributor.author","Sant, Vrinda"],["dc.contributor.author","Tekwani Movellan, Kumar"],["dc.contributor.author","Mey, Ingo P."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Steinem, Claudia"],["dc.contributor.author","Becker, Stefan T."],["dc.contributor.author","Andreas, Loren B."],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2021-06-01T09:42:06Z"],["dc.date.available","2021-06-01T09:42:06Z"],["dc.date.issued","2021"],["dc.description.abstract","Recent advances in the structural biology of disease-relevant α-synuclein fibrils have revealed a variety of structures, yet little is known about the process of fibril aggregate formation. Characterization of intermediate species that form during aggregation is crucial; however, this has proven very challenging because of their transient nature, heterogeneity, and low population. Here, we investigate the aggregation of α-synuclein bound to negatively charged phospholipid small unilamellar vesicles. Through a combination of kinetic and structural studies, we identify key time points in the aggregation process that enable targeted isolation of prefibrillar and early fibrillar intermediates. By using solid-state nuclear magnetic resonance, we show the gradual buildup of structural features in an α-synuclein fibril filament, revealing a segmental folding process. We identify distinct membrane-binding domains in α-synuclein aggregates, and the combined data are used to present a comprehensive mechanism of the folding of α-synuclein on lipid membranes."],["dc.identifier.doi","10.1126/sciadv.abg2174"],["dc.identifier.pmid","33990334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85143"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/259"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2375-2548"],["dc.relation.workinggroup","RG Griesinger"],["dc.relation.workinggroup","RG Steinem (Biomolecular Chemistry)"],["dc.rights","CC BY-NC 4.0"],["dc.title","Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","779"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","780"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Levin, Johannes"],["dc.contributor.author","Schmidt, Felix"],["dc.contributor.author","Boehm, Cathrin"],["dc.contributor.author","Prix, Catharina"],["dc.contributor.author","Boetzel, Kai"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.date.accessioned","2017-09-07T11:46:17Z"],["dc.date.available","2017-09-07T11:46:17Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1007/s00401-014-1265-3"],["dc.identifier.gro","3142137"],["dc.identifier.isi","000334426300011"],["dc.identifier.pmid","24615514"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12109"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4955"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","letter_note"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","575"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","595"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Wegrzynowicz, Michal"],["dc.contributor.author","Bar-On, Dana"],["dc.contributor.author","Calo’, Laura"],["dc.contributor.author","Anichtchik, Oleg"],["dc.contributor.author","Iovino, Mariangela"],["dc.contributor.author","Xia, Jing"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Dalley, Jeffrey W."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Ashery, Uri"],["dc.contributor.author","Spillantini, Maria Grazia"],["dc.date.accessioned","2020-12-10T14:10:27Z"],["dc.date.available","2020-12-10T14:10:27Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00401-019-02023-x"],["dc.identifier.pmid","31165254"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16591"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70765"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/28"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Griesinger"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson’s disease model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","255"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","263"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Heras-Garvin, Antonio"],["dc.contributor.author","Weckbecker, Daniel"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Wenning, Gregor K."],["dc.contributor.author","Stefanova, Nadia"],["dc.date.accessioned","2022-02-21T11:05:20Z"],["dc.date.available","2022-02-21T11:05:20Z"],["dc.date.issued","2019"],["dc.description.abstract","MSA is a fatal neurodegenerative disease characterized by autonomic failure and severe motor impairment. Its main pathological hallmark is the accumulation of α-synuclein in oligodendrocytes, leading to glial and neuronal dysfunction and neurodegeneration. These features are recapitulated in the PLP-hαSyn mouse model expressing human α-synuclein in oligodendrocytes. At present, there is no effective disease-modifying therapy. Previous experiments have shown that the aggregation inhibitor, anle138b, reduces neurodegeneration and behavioral deficits in mouse models of other proteinopathies."],["dc.identifier.doi","10.1002/mds.27562"],["dc.identifier.pmid","30452793"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100131"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/210"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.relation.workinggroup","RG Griesinger"],["dc.rights","CC BY 4.0"],["dc.title","Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy"],["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","e1000034"],["dc.bibliographiccitation.firstpage","399"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.lastpage","414"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Mukrasch, Marco D."],["dc.contributor.author","Bibow, Stefan"],["dc.contributor.author","Korukottu, Jegannath"],["dc.contributor.author","Jeganathan, Sadasivam"],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:47:34Z"],["dc.date.available","2017-09-07T11:47:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Alzheimer disease is characterized by abnormal protein deposits in the brain, such as extracellular amyloid plaques and intracellular neurofibrillary tangles. The tangles are made of a protein called tau comprising 441 residues in its longest isoform. Tau belongs to the class of natively unfolded proteins, binds to and stabilizes microtubules, and partially folds into an ordered beta-structure during aggregation to Alzheimer paired helical filaments (PHFs). Here we show that it is possible to overcome the size limitations that have traditionally hampered detailed nuclear magnetic resonance (NMR) spectroscopy studies of such large nonglobular proteins. This is achieved using optimal NMR pulse sequences and matching of chemical shifts from smaller segments in a divide and conquer strategy. The methodology reveals that 441-residue tau is highly dynamic in solution with a distinct domain character and an intricate network of transient long-range contacts important for pathogenic aggregation. Moreover, the single-residue view provided by the NMR analysis reveals unique insights into the interaction of tau with microtubules. Our results establish that NMR spectroscopy can provide detailed insight into the structural polymorphism of very large nonglobular proteins."],["dc.identifier.doi","10.1371/journal.pbio.1000034"],["dc.identifier.gro","3143159"],["dc.identifier.isi","000263599900018"],["dc.identifier.pmid","19226187"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8445"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/642"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1544-9173"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Structural Polymorphism of 441-Residue Tau at Single Residue Resolution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Nuclear Medicine and Molecular Imaging"],["dc.contributor.author","Kuebler, Laura"],["dc.contributor.author","Buss, Sabrina"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Schmidt, Felix"],["dc.contributor.author","Maurer, Andreas"],["dc.contributor.author","Weckbecker, Daniel"],["dc.contributor.author","Landau, Anne M."],["dc.contributor.author","Lillethorup, Thea P."],["dc.contributor.author","Bleher, Daniel"],["dc.contributor.author","Saw, Ran Sing"],["dc.contributor.author","Pichler, Bernd J."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Herfert, Kristina"],["dc.date.accessioned","2021-04-14T08:30:50Z"],["dc.date.available","2021-04-14T08:30:50Z"],["dc.date.issued","2020"],["dc.description.abstract","Purpose\r\n\r\nDeposition of misfolded alpha-synuclein (αSYN) aggregates in the human brain is one of the major hallmarks of synucleinopathies. However, a target-specific tracer to detect pathological aggregates of αSYN remains lacking. Here, we report the development of a positron emission tomography (PET) tracer based on anle138b, a compound shown to have therapeutic activity in animal models of neurodegenerative diseases.\r\nMethods\r\n\r\nSpecificity and selectivity of [3H]MODAG-001 were tested in in vitro binding assays using recombinant fibrils. After carbon-11 radiolabeling, the pharmacokinetic and metabolic profile was determined in mice. Specific binding was quantified in rats, inoculated with αSYN fibrils and using in vitro autoradiography in human brain sections of Lewy body dementia (LBD) cases provided by the Neurobiobank Munich (NBM).\r\nResults\r\n\r\n[3H]MODAG-001 revealed a very high affinity towards pure αSYN fibrils (Kd = 0.6 ± 0.1 nM) and only a moderate affinity to hTau46 fibrils (Kd = 19 ± 6.4 nM) as well as amyloid-β1–42 fibrils (Kd = 20 ± 10 nM). [11C]MODAG-001 showed an excellent ability to penetrate the mouse brain. Metabolic degradation was present, but the stability of the parent compound improved after selective deuteration of the precursor. (d3)-[11C]MODAG-001 binding was confirmed in fibril-inoculated rat striata using in vivo PET imaging. In vitro autoradiography showed no detectable binding to aggregated αSYN in human brain sections of LBD cases, most likely, because of the low abundance of aggregated αSYN against background protein.\r\nConclusion\r\n\r\nMODAG-001 provides a promising lead structure for future compound development as it combines a high affinity and good selectivity in fibril-binding assays with suitable pharmacokinetics and biodistribution properties."],["dc.identifier.doi","10.1007/s00259-020-05133-x"],["dc.identifier.pmid","33369690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83387"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/101"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1619-7089"],["dc.relation.issn","1619-7070"],["dc.relation.workinggroup","RG Griesinger"],["dc.rights","CC BY 4.0"],["dc.title","[11C]MODAG-001—towards a PET tracer targeting α-synuclein aggregates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Bartels, Martin"],["dc.contributor.author","Weckbecker, Daniel"],["dc.contributor.author","Kuhn, Peer-Hendrik"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Lichtenthaler, Stefan F."],["dc.contributor.author","Bötzel, Kai"],["dc.contributor.author","Giese, Armin"],["dc.date.accessioned","2020-12-10T18:10:13Z"],["dc.date.available","2020-12-10T18:10:13Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41598-019-45298-6"],["dc.identifier.eissn","2045-2322"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73892"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Iron-mediated aggregation and toxicity in a novel neuronal cell culture model with inducible alpha-synuclein expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","674"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","691"],["dc.bibliographiccitation.volume","156"],["dc.contributor.author","Raina, Anupam"],["dc.contributor.author","Leite, Kristian"],["dc.contributor.author","Guerin, Sofia"],["dc.contributor.author","Mahajani, Sameehan U."],["dc.contributor.author","Chakrabarti, Kalyan S."],["dc.contributor.author","Voll, Diana"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2021-04-14T08:22:53Z"],["dc.date.available","2021-04-14T08:22:53Z"],["dc.date.issued","2020"],["dc.description.abstract","A contribution of α-Synuclein (α-Syn) to etiology of Parkinson´s disease (PD) and Dementia with Lewy bodies (DLB) is currently undisputed, while the impact of the closely related β-Synuclein (β-Syn) on these disorders remains enigmatic. β-Syn has long been considered to be an attenuator of the neurotoxic effects of α-Syn, but in a rodent model of PD β-Syn induced robust neurodegeneration in dopaminergic neurons of the substantia nigra. Given that dopaminergic nigral neurons are selectively vulnerable to neurodegeneration in PD, we now investigated if dopamine can promote the neurodegenerative potential of β-Syn. We show that in cultured rodent and human neurons a dopaminergic neurotransmitter phenotype substantially enhanced β-Syn-induced neurodegeneration, irrespective if dopamine is synthesized within neurons or up-taken from extracellular space. Nuclear magnetic resonance interaction and thioflavin-T incorporation studies demonstrated that dopamine and its oxidized metabolites 3,4-dihydroxyphenylacetaldehyde (DOPAL) and dopaminochrome (DCH) directly interact with β-Syn, thereby enabling structural and functional modifications. Interaction of DCH with β-Syn inhibits its aggregation, which might result in increased levels of neurotoxic oligomeric β-Syn. Since protection of outer mitochondrial membrane integrity prevented the additive neurodegenerative effect of dopamine and β-Syn, such oligomers might act at a mitochondrial level similar to what is suggested for α-Syn. In conclusion, our results suggest that β-Syn can play a significant pathophysiological role in etiology of PD through its interaction with dopamine metabolites and thus should be re-considered as a disease-relevant factor, at least for those symptoms of PD that depend on degeneration of nigral dopaminergic neurons."],["dc.identifier.doi","10.1111/jnc.15134"],["dc.identifier.pmid","32730640"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80727"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/64"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.relation.workinggroup","RG Bähr (Neurobiological Research Laboratory)"],["dc.relation.workinggroup","RG Griesinger"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Dopamine promotes the neurodegenerative potential of β‐synuclein"],["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","99"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fellner, Lisa"],["dc.contributor.author","Kuzdas-Wood, Daniela"],["dc.contributor.author","Levin, Johannes"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Wenning, Gregor K."],["dc.contributor.author","Stefanova, Nadia"],["dc.date.accessioned","2017-09-07T11:54:34Z"],["dc.date.available","2017-09-07T11:54:34Z"],["dc.date.issued","2016"],["dc.description.abstract","The neurodegenerative disorder multiple system atrophy (MSA) is characterized by autonomic failure, cerebellar ataxia and parkinsonism in any combination associated with predominantly oligodendroglial alpha-synuclein (alpha-syn) aggregates (glial cytoplasmic inclusions = GCls). To date, there is no effective disease modifying therapy. Previous experiments have shown that the aggregation inhibitor anle138b reduces neurodegeneration, as well as behavioral deficits in both transgenic and toxin mouse models of Parkinson's disease (PD). Here we analyzed whether anle138b improves motor skills and reduces neuronal loss, as well as oligodendroglial alpha-syn aggregation in the PLP-alpha-syn transgenic mouse challenged with the mitochondria' toxin 3-nitropropionic acid (3-NP) to model full-blown MSA. Following 1 month of treatment with anle138b, MSA mice showed signs of motor improvement affecting stride length, but not pole, grip strength, and beam test performance. Loss of dopaminergic nigral neurons and Purkinje cells was not attenuated and GCI density remained unchanged. These data suggest that the pathology in transgenic PLP-alpha-syn mice receiving 3-NP might be too advanced to detect significant effects of anle138b treatment on neuronal loss and intracytoplasmic alpha-syn inclusion bodies. However, the partial motor amelioration may indicate potential efficacy of anle138b treatment that may be mediated by its actions on alpha-syn oligomers or may reflect improvement of neuronal dysfunction in neural at risk populations. Further studies are required to address the efficacy of anle138b in transgenic alpha-syn models of early-stage MSA and in the absence of additional toxin application."],["dc.identifier.doi","10.3389/fnins.2016.00099"],["dc.identifier.gro","3141710"],["dc.identifier.isi","000371761400001"],["dc.identifier.pmid","27013960"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/213"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1662-453X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]