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| Home > Publications Database > Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies. > print |
| 001 | 138183 | ||
| 005 | 20240321220404.0 | ||
| 024 | 7 | _ | |a 10.2174/156720501209151019104951 |2 doi |
| 024 | 7 | _ | |a pmid:26510979 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC4976804 |2 pmc |
| 024 | 7 | _ | |a 1567-2050 |2 ISSN |
| 024 | 7 | _ | |a 1875-5828 |2 ISSN |
| 024 | 7 | _ | |a altmetric:4705877 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-04505 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Pickhardt, Marcus |0 P:(DE-2719)2810282 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies. |
| 260 | _ | _ | |a Hilversum |c 2015 |b Bentham Science Publ. Ltd. |
| 264 | _ | 1 | |3 print |2 Crossref |b Bentham Science Publishers Ltd. |c 2015-10-19 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1593521440_30453 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a A 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. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Benzothiazoles |2 NLM Chemicals |
| 650 | _ | 7 | |a Fluorescent Dyes |2 NLM Chemicals |
| 650 | _ | 7 | |a MAPT protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Neuroprotective Agents |2 NLM Chemicals |
| 650 | _ | 7 | |a Protein Aggregates |2 NLM Chemicals |
| 650 | _ | 7 | |a Thiazoles |2 NLM Chemicals |
| 650 | _ | 7 | |a tau Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a thioflavin T |0 2390-54-7 |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Benzothiazoles |2 MeSH |
| 650 | _ | 2 | |a Cell Line, Tumor |2 MeSH |
| 650 | _ | 2 | |a Cell Survival: drug effects |2 MeSH |
| 650 | _ | 2 | |a Dose-Response Relationship, Drug |2 MeSH |
| 650 | _ | 2 | |a Drug Evaluation, Preclinical |2 MeSH |
| 650 | _ | 2 | |a Fluorescent Dyes |2 MeSH |
| 650 | _ | 2 | |a High-Throughput Screening Assays |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Microarray Analysis |2 MeSH |
| 650 | _ | 2 | |a Microscopy, Fluorescence |2 MeSH |
| 650 | _ | 2 | |a Molecular Structure |2 MeSH |
| 650 | _ | 2 | |a Neuroprotective Agents: chemistry |2 MeSH |
| 650 | _ | 2 | |a Neuroprotective Agents: pharmacology |2 MeSH |
| 650 | _ | 2 | |a Protein Aggregates: drug effects |2 MeSH |
| 650 | _ | 2 | |a Protein Multimerization: drug effects |2 MeSH |
| 650 | _ | 2 | |a Tauopathies: drug therapy |2 MeSH |
| 650 | _ | 2 | |a Tauopathies: metabolism |2 MeSH |
| 650 | _ | 2 | |a Thiazoles |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: metabolism |2 MeSH |
| 700 | 1 | _ | |a Neumann, Thomas |b 1 |
| 700 | 1 | _ | |a Schwizer, Daniel |b 2 |
| 700 | 1 | _ | |a Callaway, Kari |b 3 |
| 700 | 1 | _ | |a Vendruscolo, Michele |b 4 |
| 700 | 1 | _ | |a Schenk, Dale |b 5 |
| 700 | 1 | _ | |a St George-Hyslop, Peter |b 6 |
| 700 | 1 | _ | |a Mandelkow, Eva M |0 P:(DE-2719)2541658 |b 7 |u dzne |
| 700 | 1 | _ | |a Dobson, Christopher M |b 8 |
| 700 | 1 | _ | |a McConlogue, Lisa |b 9 |
| 700 | 1 | _ | |a Mandelkow, Eckhard |0 P:(DE-2719)2541671 |b 10 |u dzne |
| 700 | 1 | _ | |a Tóth, Gergely |0 P:(DE-HGF)0 |b 11 |e Corresponding author |
| 773 | 1 | 8 | |a 10.2174/156720501209151019104951 |b : Bentham Science Publishers Ltd., 2015-10-19 |n 9 |p 814-828 |3 journal-article |2 Crossref |t Current Alzheimer Research |v 12 |y 2015 |x 1567-2050 |
| 773 | _ | _ | |a 10.2174/156720501209151019104951 |g Vol. 12, no. 9, p. 814 - 828 |0 PERI:(DE-600)2155964-8 |n 9 |q 12:9<814 - 828 |p 814-828 |t Current Alzheimer research |v 12 |y 2015 |x 1567-2050 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976804 |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 0 |6 P:(DE-2719)2810282 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 7 |6 P:(DE-2719)2541658 |
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| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b CURR ALZHEIMER RES : 2017 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0111 |2 StatID |b Science Citation Index Expanded |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |
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| 915 | _ | _ | |a IF < 5 |0 StatID:(DE-HGF)9900 |2 StatID |
| 920 | 1 | _ | |0 I:(DE-2719)1013014 |k AG Mandelkow 1 |l Structural Principles of Neurodegeneration |x 0 |
| 920 | 1 | _ | |0 I:(DE-2719)1013015 |k AG Mandelkow 2 |l Cell and Animal Models of Neurodegeneration |x 1 |
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| 980 | _ | _ | |a UNRESTRICTED |
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