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000138181 0247_ $$2pmc$$apmc:PMC4612332
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000138181 0247_ $$2ISSN$$a1432-0533
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000138181 037__ $$aDZNE-2020-04503
000138181 041__ $$aEnglish
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000138181 1001_ $$0P:(DE-2719)2662292$$aWagner, Jens$$b0$$eFirst author
000138181 245__ $$aReducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies.
000138181 260__ $$aHeidelberg$$bSpringer$$c2015
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000138181 520__ $$aPathological tau aggregation leads to filamentous tau inclusions and characterizes neurodegenerative tauopathies such as Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation coincides with clinical symptoms and is thought to mediate neurodegeneration. Transgenic mice overexpressing mutant human P301S tau exhibit many neuropathological features of human tauopathies including behavioral deficits and increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore, anle138b treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice. In addition, we found decreased synapse and neuron loss accompanied by a decreased gliosis in the hippocampus. Our results suggest that reducing tau aggregates with anle138b may represent an effective and promising approach for the treatment of human tauopathies.
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000138181 650_7 $$2NLM Chemicals$$a3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole
000138181 650_7 $$2NLM Chemicals$$aBenzodioxoles
000138181 650_7 $$2NLM Chemicals$$aMAPT protein, human
000138181 650_7 $$2NLM Chemicals$$aMapt protein, mouse
000138181 650_7 $$2NLM Chemicals$$aNeuroprotective Agents
000138181 650_7 $$2NLM Chemicals$$aProtein Aggregates
000138181 650_7 $$2NLM Chemicals$$aPyrazoles
000138181 650_7 $$2NLM Chemicals$$atau Proteins
000138181 650_2 $$2MeSH$$aAnimals
000138181 650_2 $$2MeSH$$aBenzodioxoles: pharmacology
000138181 650_2 $$2MeSH$$aCell Death: drug effects
000138181 650_2 $$2MeSH$$aCell Death: physiology
000138181 650_2 $$2MeSH$$aDisease Models, Animal
000138181 650_2 $$2MeSH$$aDisease Progression
000138181 650_2 $$2MeSH$$aFemale
000138181 650_2 $$2MeSH$$aGliosis: drug therapy
000138181 650_2 $$2MeSH$$aGliosis: pathology
000138181 650_2 $$2MeSH$$aGliosis: physiopathology
000138181 650_2 $$2MeSH$$aHippocampus: drug effects
000138181 650_2 $$2MeSH$$aHippocampus: pathology
000138181 650_2 $$2MeSH$$aHippocampus: physiopathology
000138181 650_2 $$2MeSH$$aMale
000138181 650_2 $$2MeSH$$aMice, Transgenic
000138181 650_2 $$2MeSH$$aMotor Activity: drug effects
000138181 650_2 $$2MeSH$$aMotor Activity: physiology
000138181 650_2 $$2MeSH$$aNeurons: drug effects
000138181 650_2 $$2MeSH$$aNeurons: pathology
000138181 650_2 $$2MeSH$$aNeurons: physiology
000138181 650_2 $$2MeSH$$aNeuroprotective Agents: pharmacology
000138181 650_2 $$2MeSH$$aProtein Aggregates: drug effects
000138181 650_2 $$2MeSH$$aPyrazoles: pharmacology
000138181 650_2 $$2MeSH$$aRandom Allocation
000138181 650_2 $$2MeSH$$aRecognition, Psychology: drug effects
000138181 650_2 $$2MeSH$$aRecognition, Psychology: physiology
000138181 650_2 $$2MeSH$$aTauopathies: drug therapy
000138181 650_2 $$2MeSH$$aTauopathies: pathology
000138181 650_2 $$2MeSH$$atau Proteins: genetics
000138181 650_2 $$2MeSH$$atau Proteins: metabolism
000138181 7001_ $$0P:(DE-2719)2421562$$aKrauß, Sybille$$b1
000138181 7001_ $$0P:(DE-HGF)0$$aShi, Song$$b2
000138181 7001_ $$0P:(DE-HGF)0$$aRyazanov, Sergey$$b3
000138181 7001_ $$0P:(DE-2719)2810279$$aSteffen, Julia$$b4
000138181 7001_ $$0P:(DE-2719)2810438$$aMiklitz, Carolin$$b5
000138181 7001_ $$0P:(DE-HGF)0$$aLeonov, Andrei$$b6
000138181 7001_ $$0P:(DE-HGF)0$$aKleinknecht, Alexander$$b7
000138181 7001_ $$0P:(DE-HGF)0$$aGöricke, Bettina$$b8
000138181 7001_ $$0P:(DE-HGF)0$$aWeishaupt, Jochen H$$b9
000138181 7001_ $$0P:(DE-HGF)0$$aWeckbecker, Daniel$$b10
000138181 7001_ $$0P:(DE-HGF)0$$aReiner, Anne M$$b11
000138181 7001_ $$0P:(DE-HGF)0$$aZinth, Wolfgang$$b12
000138181 7001_ $$0P:(DE-HGF)0$$aLevin, Johannes$$b13
000138181 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b14
000138181 7001_ $$0P:(DE-2719)2810375$$aRemy, Stefan$$b15
000138181 7001_ $$0P:(DE-HGF)0$$aKretzschmar, Hans A$$b16
000138181 7001_ $$0P:(DE-HGF)0$$aGriesinger, Christian$$b17
000138181 7001_ $$0P:(DE-HGF)0$$aGiese, Armin$$b18
000138181 7001_ $$0P:(DE-2719)2679991$$aFuhrmann, Martin$$b19$$eLast author
000138181 77318 $$2Crossref$$3journal-article$$a10.1007/s00401-015-1483-3$$b : Springer Science and Business Media LLC, 2015-10-06$$n5$$p619-631$$tActa Neuropathologica$$v130$$x0001-6322$$y2015
000138181 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-015-1483-3$$gVol. 130, no. 5, p. 619 - 631$$n5$$p619-631$$q130:5<619 - 631$$tActa neuropathologica$$v130$$x0001-6322$$y2015
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