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Inhibition of tau aggregation by a rosamine derivative that blocks tau intermolecular disulfide cross-linking
- Source :
- Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 21(3)
- Publication Year :
- 2014
-
Abstract
- Abnormal tau aggregates are presumed to be neurotoxic and are an important therapeutic target for multiple neurodegenerative disorders including Alzheimer’s disease. Growing evidence has shown that tau intermolecular disulfide cross-linking is critical in generating tau oligomers that serve as a building block for higher-order aggregates. Here we report that a small molecule inhibitor prevents tau aggregation by blocking the generation of disulfide cross-linked tau oligomers. Among the compounds tested, a rosamine derivative bearing mild thiol reactivity selectively labeled tau and effectively inhibited oligomerization and fibrillization processes in vitro. Our data suggest that controlling tau oxidation status could be a new therapeutic strategy for prevention of abnormal tau aggregation.
- Subjects :
- Tau protein
Gene Expression
tau Proteins
Small Molecule Libraries
chemistry.chemical_compound
Protein Aggregates
mental disorders
Drug Discovery
Internal Medicine
medicine
Escherichia coli
Humans
Benzothiazoles
Disulfides
Fluorescent Dyes
chemistry.chemical_classification
biology
Neurodegeneration
Intermolecular force
Disulfide bond
medicine.disease
Small molecule
In vitro
Peptide Fragments
Recombinant Proteins
Solutions
Thiazoles
Spectrometry, Fluorescence
Biochemistry
chemistry
Xanthenes
biology.protein
Biophysics
Thiol
Protein Multimerization
Oxidation-Reduction
Derivative (chemistry)
Subjects
Details
- ISSN :
- 17442818
- Volume :
- 21
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
- Accession number :
- edsair.doi.dedup.....6a9d0bc602372c270309cf128037a54c