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

Wen Bo Yu; Teng Jiang; Dan Mei Lan; Jia Hong Lu; Zhen Yu Yue; Jian Wang; Ping Zhou

doi:10.1016/j.abb.2012.04.021

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

Wen Bo Yu
, Teng Jiang
, Dan Mei Lan
, Jia Hong Lu
, Zhen Yu Yue
, Jian Wang
, Ping Zhou

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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.

Original language	English
Pages (from-to)	144-150
Number of pages	7
Journal	Archives of Biochemistry and Biophysics
Volume	523
Issue number	2
DOIs	https://doi.org/10.1016/j.abb.2012.04.021
State	Published - 15 Jul 2012

Keywords

Aggregate morphologies
Alpha-synuclein
Parkinson's disease
Protein conformation
Trehalose

Access to Document

10.1016/j.abb.2012.04.021

Cite this

@article{ae9a5d10895040b3a955f6923ac12383,

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.",

keywords = "Aggregate morphologies, Alpha-synuclein, Parkinson's disease, Protein conformation, Trehalose",

author = "Yu, \{Wen Bo\} and Teng Jiang and Lan, \{Dan Mei\} and Lu, \{Jia Hong\} and Yue, \{Zhen Yu\} and Jian Wang and Ping Zhou",

note = "Funding Information: This study was supported by the Grants (30600663, 81071018, 20673022, and 21074025) from the Natural Science Foundation of China for study design and data collection/analysis, Project (10PJ1401700) of Pujiang Talents at Shanghai for data analysis, Project (09411960900) and Science and Technology Innovation Action Plan (11DZ1971802), Science and Technology Commission of Shanghai Municipality for the expense of collaboration. We are grateful for the technical assistance from Dr. Hao Liu and Guodong Cao at the University of Pittsburgh School of Medicine, editorial assistance from Dr. Ruth G. Perez at Texas Tech Paul L Foster School of Medicine in El Paso and helpful discussion from Prof. Yuping Jiang at Huashan Hospital Affiliated to Fudan University at Shanghai.",

year = "2012",

month = jul,

day = "15",

doi = "10.1016/j.abb.2012.04.021",

language = "English",

volume = "523",

pages = "144--150",

journal = "Archives of Biochemistry and Biophysics",

issn = "0003-9861",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils

AU - Yu, Wen Bo

AU - Jiang, Teng

AU - Lan, Dan Mei

AU - Lu, Jia Hong

AU - Yue, Zhen Yu

AU - Wang, Jian

AU - Zhou, Ping

N1 - Funding Information: This study was supported by the Grants (30600663, 81071018, 20673022, and 21074025) from the Natural Science Foundation of China for study design and data collection/analysis, Project (10PJ1401700) of Pujiang Talents at Shanghai for data analysis, Project (09411960900) and Science and Technology Innovation Action Plan (11DZ1971802), Science and Technology Commission of Shanghai Municipality for the expense of collaboration. We are grateful for the technical assistance from Dr. Hao Liu and Guodong Cao at the University of Pittsburgh School of Medicine, editorial assistance from Dr. Ruth G. Perez at Texas Tech Paul L Foster School of Medicine in El Paso and helpful discussion from Prof. Yuping Jiang at Huashan Hospital Affiliated to Fudan University at Shanghai.

PY - 2012/7/15

Y1 - 2012/7/15

N2 - 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.

AB - 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.

KW - Aggregate morphologies

KW - Alpha-synuclein

KW - Parkinson's disease

KW - Protein conformation

KW - Trehalose

UR - https://www.scopus.com/pages/publications/84861899099

U2 - 10.1016/j.abb.2012.04.021

DO - 10.1016/j.abb.2012.04.021

M3 - Article

C2 - 22575388

AN - SCOPUS:84861899099

SN - 0003-9861

VL - 523

SP - 144

EP - 150

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

IS - 2

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this