Osmolytes modulate polyglutamine aggregation in a sequence dependent manner |
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Authors: | Itika Saha Virender Singh Gunasekhar Burra Ashwani Kumar Thakur |
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Institution: | 1. Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany;2. Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, India |
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Abstract: | Osmolytes stabilize protein structure and suppress protein aggregation. The mechanism of how osmolytes impact polyglutamine (polyQ) aggregation implicated in Huntington's disease was studied. By using a reverse‐phase chromatography assay, we show that methylamines‐trimethylamine N‐oxide and betaine are generic in enhancing polyQ aggregation, while a disaccharide trehalose and an amino acid citrulline moderately retard polyQ aggregation in a sequence specific manner. Despite the altered kinetics, the fundamental nucleation mechanism of polyQ aggregation and the nature of end stage aggregates remains unaffected. These results highlight the importance of using osmolytes as modulatory agents of polyQ aggregation. |
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Keywords: | Huntington's disease osmolytes polyglutamine aggregation |
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