Inhibition of tau aggregation by a rosamine derivative that blocks tau intermolecular disulfide cross-linking. (September 2014)

• Record Type: Journal Article
• Authors: Haque, Md. Mamunul; Kim, Dohee; Yu, Young Hyun; Lim, Sungsu; Kim, Dong Jin; Chang, Young-Tae; Ha, Hyung-Ho; Kim, Yun Kyung
• Is Part Of: Amyloid. Volume 21:Number 3(2014)
• Page Start: 185
• Page End: 190
• Publication Date: 2014-09
• Subjects: Amyloidosis -- Periodicals; 616.3995
• DOI: 10.3109/13506129.2014.929103
• Languages: English
• ISSNs: 1350-6129

Abstract

<abstract> <title>Abstract</title> <p>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 <italic>in vitro</italic>. Our data suggest that controlling tau oxidation status could be a new therapeutic strategy for prevention of abnormal tau aggregation.</p> </abstract>