Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson's disease and multiple system atrophy

被引：31

作者：

Klingstedt, Therese ^{[1
,4
]}

Ghetti, Bernardino ^{[2
]}

Holton, Janice L. ^{[3
]}

Ling, Helen ^{[3
]}

Nilsson, K. Peter R. ^{[4
]}

Goedert, Michel ^{[1
]}

机构：

[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England

[2] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA

[3] UCL Queen Sq Inst Neurol, Queen Sq Brain Bank, London WC1N 1PJ, England

[4] Linkoping Univ, Dept Phys Chem & Biol, S-58183 Linkoping, Sweden

来源：

ACTA NEUROPATHOLOGICA COMMUNICATIONS | 2019年 / 7卷 / 01期

基金：

英国医学研究理事会; 瑞典研究理事会;

关键词：

alpha-Synuclein; Luminescent conjugated oligothiophene; Multiple system atrophy; Neurodegeneration; Parkinson's disease; Spectral analysis; GLIAL CYTOPLASMIC INCLUSIONS; SPECTRAL ASSIGNMENT; LEWY BODIES; LIGANDS; DEMENTIA; FILAMENTS; PLETHORA;

D O I：

10.1186/s40478-019-0840-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Synucleinopathies [Parkinson's disease with or without dementia, dementia with Lewy bodies and multiple system atrophy] are neurodegenerative diseases that are defined by the presence of filamentous alpha-synuclein inclusions. We investigated the ability of luminescent conjugated oligothiophenes to stain the inclusions of Parkinson's disease and multiple system atrophy. They stained the Lewy pathology of Parkinson's disease and the glial cytoplasmic inclusions of multiple system atrophy. Spectral analysis of HS-68-stained inclusions showed a red shift in multiple system atrophy, but the difference with Parkinson's disease was not significant. However, when inclusions were double-labelled for HS-68 and an antibody specific for alpha-synuclein phosphorylated at S129, they could be distinguished based on colour shifts with blue designated for Parkinson's disease and red for multiple system atrophy. The inclusions of Parkinson's disease and multiple system atrophy could also be distinguished using fluorescence lifetime imaging. These findings are consistent with the presence of distinct conformers of assembled a-synuclein in Parkinson's disease and multiple system atrophy.

引用

页数：9

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