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000138183 0247_ $$2doi$$a10.2174/156720501209151019104951
000138183 0247_ $$2pmid$$apmid:26510979
000138183 0247_ $$2pmc$$apmc:PMC4976804
000138183 0247_ $$2ISSN$$a1567-2050
000138183 0247_ $$2ISSN$$a1875-5828
000138183 0247_ $$2altmetric$$aaltmetric:4705877
000138183 037__ $$aDZNE-2020-04505
000138183 041__ $$aEnglish
000138183 082__ $$a610
000138183 1001_ $$0P:(DE-2719)2810282$$aPickhardt, Marcus$$b0$$eFirst author$$udzne
000138183 245__ $$aIdentification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies.
000138183 260__ $$aHilversum$$bBentham Science Publ. Ltd.$$c2015
000138183 264_1 $$2Crossref$$3print$$bBentham Science Publishers Ltd.$$c2015-10-19
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000138183 520__ $$aA potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer's and Parkinson's diseases.
000138183 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
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000138183 650_7 $$2NLM Chemicals$$aBenzothiazoles
000138183 650_7 $$2NLM Chemicals$$aFluorescent Dyes
000138183 650_7 $$2NLM Chemicals$$aMAPT protein, human
000138183 650_7 $$2NLM Chemicals$$aNeuroprotective Agents
000138183 650_7 $$2NLM Chemicals$$aProtein Aggregates
000138183 650_7 $$2NLM Chemicals$$aThiazoles
000138183 650_7 $$2NLM Chemicals$$atau Proteins
000138183 650_7 $$02390-54-7$$2NLM Chemicals$$athioflavin T
000138183 650_2 $$2MeSH$$aAnimals
000138183 650_2 $$2MeSH$$aBenzothiazoles
000138183 650_2 $$2MeSH$$aCell Line, Tumor
000138183 650_2 $$2MeSH$$aCell Survival: drug effects
000138183 650_2 $$2MeSH$$aDose-Response Relationship, Drug
000138183 650_2 $$2MeSH$$aDrug Evaluation, Preclinical
000138183 650_2 $$2MeSH$$aFluorescent Dyes
000138183 650_2 $$2MeSH$$aHigh-Throughput Screening Assays
000138183 650_2 $$2MeSH$$aHumans
000138183 650_2 $$2MeSH$$aMice
000138183 650_2 $$2MeSH$$aMicroarray Analysis
000138183 650_2 $$2MeSH$$aMicroscopy, Fluorescence
000138183 650_2 $$2MeSH$$aMolecular Structure
000138183 650_2 $$2MeSH$$aNeuroprotective Agents: chemistry
000138183 650_2 $$2MeSH$$aNeuroprotective Agents: pharmacology
000138183 650_2 $$2MeSH$$aProtein Aggregates: drug effects
000138183 650_2 $$2MeSH$$aProtein Multimerization: drug effects
000138183 650_2 $$2MeSH$$aTauopathies: drug therapy
000138183 650_2 $$2MeSH$$aTauopathies: metabolism
000138183 650_2 $$2MeSH$$aThiazoles
000138183 650_2 $$2MeSH$$atau Proteins: genetics
000138183 650_2 $$2MeSH$$atau Proteins: metabolism
000138183 7001_ $$aNeumann, Thomas$$b1
000138183 7001_ $$aSchwizer, Daniel$$b2
000138183 7001_ $$aCallaway, Kari$$b3
000138183 7001_ $$aVendruscolo, Michele$$b4
000138183 7001_ $$aSchenk, Dale$$b5
000138183 7001_ $$aSt George-Hyslop, Peter$$b6
000138183 7001_ $$0P:(DE-2719)2541658$$aMandelkow, Eva M$$b7$$udzne
000138183 7001_ $$aDobson, Christopher M$$b8
000138183 7001_ $$aMcConlogue, Lisa$$b9
000138183 7001_ $$0P:(DE-2719)2541671$$aMandelkow, Eckhard$$b10$$udzne
000138183 7001_ $$0P:(DE-HGF)0$$aTóth, Gergely$$b11$$eCorresponding author
000138183 77318 $$2Crossref$$3journal-article$$a10.2174/156720501209151019104951$$b : Bentham Science Publishers Ltd., 2015-10-19$$n9$$p814-828$$tCurrent Alzheimer Research$$v12$$x1567-2050$$y2015
000138183 773__ $$0PERI:(DE-600)2155964-8$$a10.2174/156720501209151019104951$$gVol. 12, no. 9, p. 814 - 828$$n9$$p814-828$$q12:9<814 - 828$$tCurrent Alzheimer research$$v12$$x1567-2050$$y2015
000138183 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976804
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000138183 9141_ $$y2015
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