title: 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.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Yu
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.forename: Dan-Mei
authors.initials: DM
authors.lastname: Lan
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Lu
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Yue
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
mesh_terms: D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D014199:Trehalose / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D051844:alpha-Synuclein; D014199:Trehalose