Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils.

Abstract

The aggregation of alpha-synuclein (AS) is pivotally implicated in the development of Parkinson's disease (PD), inhibiting this process might be effective in treating PD. Here, by using circular dichroism spectroscopy, thioflavin T fluorescence, and atomic force microscopy, we found that trehalose at low concentration disaggregates preformed A53T AS protofibrils and fibrils into small aggregates or even random coil structure, while trehalose at high concentration slows down the structural transition into β-sheet structure and completely prevents the formation of mature A53T AS fibrils. Further work in vivo will be needed to evaluate its potential as a novel strategy for treating PD.

• Authors: Wen-Bo Yu, Teng Jiang, Dan-Mei Lan, Jia-Hong Lu, Zhen-Yu Yue, Jian Wang, Ping Zhou
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 523 Issue 2 Pg. 144-50 (Jul 15 2012) ISSN: 1096-0384 [Electronic] United States
• PMID: 22575388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Mutant Proteins
• alpha-Synuclein
• Trehalose

Topics

• Humans
• Models, Molecular
• Mutant Proteins (chemistry, genetics)
• Mutation
• Protein Multimerization (drug effects)
• Protein Structure, Secondary (drug effects)
• Trehalose (pharmacology)
• alpha-Synuclein (chemistry, genetics)