001     138181
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024 7 _ |a 10.1007/s00401-015-1483-3
|2 doi
024 7 _ |a pmid:26439832
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024 7 _ |a pmc:PMC4612332
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024 7 _ |a 0001-6322
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024 7 _ |a 1432-0533
|2 ISSN
024 7 _ |a altmetric:4594501
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037 _ _ |a DZNE-2020-04503
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Wagner, Jens
|0 P:(DE-2719)2662292
|b 0
|e First author
245 _ _ |a Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies.
260 _ _ |a Heidelberg
|c 2015
|b Springer
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2015-10-06
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2015-11-01
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a Pathological tau aggregation leads to filamentous tau inclusions and characterizes neurodegenerative tauopathies such as Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation coincides with clinical symptoms and is thought to mediate neurodegeneration. Transgenic mice overexpressing mutant human P301S tau exhibit many neuropathological features of human tauopathies including behavioral deficits and increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore, anle138b treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice. In addition, we found decreased synapse and neuron loss accompanied by a decreased gliosis in the hippocampus. Our results suggest that reducing tau aggregates with anle138b may represent an effective and promising approach for the treatment of human tauopathies.
536 _ _ |a 341 - Molecular Signaling (POF3-341)
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|f POF III
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a 3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole
|2 NLM Chemicals
650 _ 7 |a Benzodioxoles
|2 NLM Chemicals
650 _ 7 |a MAPT protein, human
|2 NLM Chemicals
650 _ 7 |a Mapt protein, mouse
|2 NLM Chemicals
650 _ 7 |a Neuroprotective Agents
|2 NLM Chemicals
650 _ 7 |a Protein Aggregates
|2 NLM Chemicals
650 _ 7 |a Pyrazoles
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Benzodioxoles: pharmacology
|2 MeSH
650 _ 2 |a Cell Death: drug effects
|2 MeSH
650 _ 2 |a Cell Death: physiology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Disease Progression
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Gliosis: drug therapy
|2 MeSH
650 _ 2 |a Gliosis: pathology
|2 MeSH
650 _ 2 |a Gliosis: physiopathology
|2 MeSH
650 _ 2 |a Hippocampus: drug effects
|2 MeSH
650 _ 2 |a Hippocampus: pathology
|2 MeSH
650 _ 2 |a Hippocampus: physiopathology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Motor Activity: drug effects
|2 MeSH
650 _ 2 |a Motor Activity: physiology
|2 MeSH
650 _ 2 |a Neurons: drug effects
|2 MeSH
650 _ 2 |a Neurons: pathology
|2 MeSH
650 _ 2 |a Neurons: physiology
|2 MeSH
650 _ 2 |a Neuroprotective Agents: pharmacology
|2 MeSH
650 _ 2 |a Protein Aggregates: drug effects
|2 MeSH
650 _ 2 |a Pyrazoles: pharmacology
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650 _ 2 |a Random Allocation
|2 MeSH
650 _ 2 |a Recognition, Psychology: drug effects
|2 MeSH
650 _ 2 |a Recognition, Psychology: physiology
|2 MeSH
650 _ 2 |a Tauopathies: drug therapy
|2 MeSH
650 _ 2 |a Tauopathies: pathology
|2 MeSH
650 _ 2 |a tau Proteins: genetics
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
700 1 _ |a Krauß, Sybille
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700 1 _ |a Shi, Song
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700 1 _ |a Ryazanov, Sergey
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700 1 _ |a Steffen, Julia
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700 1 _ |a Miklitz, Carolin
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700 1 _ |a Leonov, Andrei
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700 1 _ |a Kleinknecht, Alexander
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700 1 _ |a Göricke, Bettina
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700 1 _ |a Weishaupt, Jochen H
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700 1 _ |a Weckbecker, Daniel
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700 1 _ |a Reiner, Anne M
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700 1 _ |a Zinth, Wolfgang
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700 1 _ |a Levin, Johannes
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700 1 _ |a Ehninger, Dan
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700 1 _ |a Remy, Stefan
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700 1 _ |a Kretzschmar, Hans A
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700 1 _ |a Griesinger, Christian
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700 1 _ |a Giese, Armin
|0 P:(DE-HGF)0
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700 1 _ |a Fuhrmann, Martin
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773 1 8 |a 10.1007/s00401-015-1483-3
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|y 2015
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773 _ _ |a 10.1007/s00401-015-1483-3
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856 4 _ |y OpenAccess
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Marc 21